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BACKGROUND/OBJECTIVES@#Benign prostatic hyperplasia (BPH) characterized by an enlarged prostate gland is common in elderly men. Corni Fructus (CF) and Schisandrae Fructus (SF) are known to have various pharmacological effects, including antioxidant and anti-inflammatory activities. In this study, we evaluated the inhibitory efficacy of CF, SF, and their mixture (MIX) on the development of BPH using an in vivo model of testosteroneinduced BPH.MATERIALS/METHODS: Six-week-old male Sprague-Dawley rats were randomly divided into seven groups. To induce BPH, testosterone propionate (TP) was injected to rats except for those in the control group. Finasteride, saw palmetto (SP), CF, SF, and MIX were orally administered along with TP injection. At the end of treatment, histological changes in the prostate and the level of various biomarkers related to BPH were evaluated. @*RESULTS@#Our results showed that BPH induced by TP led to prostate weight and histological changes. Treatment with MIX effectively improved TP-induced BPH by reducing prostate index, lumen area, epithelial thickness, and expression of BPH biomarkers such as 5α-reductase type 2, prostate-specific antigen, androgen receptor, and proliferating cell nuclear antigen compared to treatment with CF or SF alone. Moreover, MIX further reduced levels of elevated serum testosterone, dihydrotestosterone, and prostate-specific antigen in BPH compared to the SP, a positive control. BPH was also improved more by MIX than by CF or SF alone. @*CONCLUSIONS@#Based on the results, MIX is a potential natural therapeutic candidate for BPH by regulating 5α-reductase and AR signaling pathway.
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BACKGROUND/OBJECTIVES@#Zanthoxylum schinifolium is traditionally used as a spice for cooking in East Asian countries. This study was undertaken to evaluate the anti-proliferative potential of ethanol extracts of Z. schinifolium leaves (EEZS) against human bladder cancer T24 cells.MATERIALS/METHODS: Subsequent to measuring the cytotoxicity of EEZS, the anti-cancer activity was measured by assessing apoptosis induction, reactive oxygen species (ROS) generation, and mitochondrial membrane potential (MMP). In addition, we determined the underlying mechanism of EEZS-induced apoptosis through various assays, including Western blot analysis. @*RESULTS@#EEZS treatment concentration-dependently inhibited T24 cell survival, which is associated with apoptosis induction. Exposure to EEZS induced the expression of Fas and Fas-ligand, activated caspases, and subsequently resulted to cleavage of poly (ADPribose) polymerase. EEZS also enhanced the expression of cytochrome c in the cytoplasm by suppressing MMP, following increase in the ratio of Bax:Bcl-2 expression and truncation of Bid. However, EEZS-mediated growth inhibition and apoptosis were significantly diminished by a pan-caspase inhibitor. Moreover, EEZS inhibited activation of the phosphoinositide 3-kinase (PI3K)/Akt pathway, and the apoptosis-inducing potential of EEZS was promoted in the presence of PI3K/Akt inhibitor. In addition, EEZS enhanced the production of ROS, whereas N-acetyl cysteine (NAC), a ROS scavenger, markedly suppressed growth inhibition and inactivation of the PI3K/Akt signaling pathway induced by EEZS. Furthermore, NAC significantly attenuated the EEZS-induced apoptosis and reduction of cell viability. @*CONCLUSIONS@#Taken together, our results indicate that exposure to EEZS exhibits anticancer activity in T24 bladder cancer cells through ROS-dependent induction of apoptosis and inactivation of the PI3K/Akt signaling pathway.
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BACKGROUND/OBJECTIVES@#Schisandrae Fructus, the fruit of Schisandra chinensis Baill., has traditionally been used as a medicinal herb for the treatment of various diseases, and has proven its various pharmacological effects, including anti-inflammatory and antioxidant activities. In this study, we investigated the inhibitory effect of Schisandrae Fructus ethanol extract (SF) on inflammatory and oxidative stress in particulate matter 2.5 (PM2.5)-treated RAW 264.7 macrophages.MATERIALS/METHODS: To investigate the anti-inflammatory and antioxidant effects of SF in PM2.5-stimulated RAW 264.7 cells, the levels of pro-inflammatory mediator such as nitric oxide (NO) and prostaglandin E2 (PGE2 ), cytokines including interleukin (IL)-6 and IL-1β, and reactive oxygen species (ROS) were measured. To elucidate the mechanism underlying the effect of SF, the expression of genes involved in the generation of inflammatory factors was also investigated. We further evaluated the anti-inflammatory and antioxidant efficacy of SF against PM2.5 in the zebrafish model. @*RESULTS@#The results indicated that SF treatment significantly inhibited the PM2.5-induced release of NO and PGE2 , which was associated with decreased inducible NO synthase and cyclooxygenase-2 expression. SF also attenuated the PM2.5-induced expression of IL-6 and IL-1β, reducing their extracellular secretion. Moreover, SF suppressed the PM2.5-mediated translocation of nuclear factor-kappa B (NF-κB) from the cytosol into nuclei and the degradation of inhibitor IκB-α, indicating that SF exhibited anti-inflammatory effects by inhibiting the NF-κB signaling pathway. In addition, SF abolished PM2.5-induced generation of ROS, similar to the pretreatment of a ROS scavenger, but not by an inhibitor of NF-κB activity. Furthermore, SF showed strong protective effects against NO and ROS production in PM2.5-treated zebrafish larvae. @*CONCLUSIONS@#Our findings suggest that SF exerts anti-inflammatory and antioxidant effects against PM2.5 through ROS-dependent down-regulating the NF-κB signaling pathway, and that SF can be a potential functional substance to prevent PM2.5-mediated inflammatory and oxidative damage.
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Objective: To investigate whether the ethanol extract of Chondracanthus tenellus (Harvey) Hommersand, a type of red algae, could exhibit anti-inflammatory potential in lipopolysaccharide (LPS)-stimulated macrophages. Methods: The ethanol extract of Chondracanthus tenellus was applied to 100 ng/mL LPS-stimulated RAW 264.7 cells, and cell viability, phagocytic ability, levels of pro-inflammatory factors, and the production of reactive oxygen species were measured. To identify the underlying mechanism of the ethanol extract of Chondracanthus tenellus, the expression of inflammation-regulated genes was estimated. Results: The ethanol extract of Chondracanthus tenellus had no cytotoxic effect at concentrations below 300 μg/mL, and reduced the LPS-induced production of inflammatory mediators including nitric oxide (NO) and prostaglandin E 2. Furthermore, the extract markedly suppressed the expression of inducible NO synthase and cyclooxygenase-2, as well as the production of reactive oxygen species. The LPS-induced up-regulation of pro-inflammatory cytokines was attenuated by treatment with the ethanol extract of Chondracanthus tenellus, reducing their extracellular secretion. The Chondracanthus tenellus extract also inhibited LPS-mediated activation of nuclear factor-kappa B (NF-κB). In addition, the phosphorylation of mitogen activated protein kinases (MAPKs) and phosphatidylinositol 3 kinase (PI3K)/Akt was markedly increased by LPS, which was significantly abolished by the Chondracanthus tenellus extract. Conclusions: Our findings indicate that the ethanol extract of Chondracanthus tenellus exhibited potential anti-inflammatory and antioxidant effects through downregulating the NF-κB, MAPKs, and PI3K/Akt signaling pathways in LPS stimulated RAW 264.7 macrophages.
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Objective: To investigate whether ethanol extracts of Chondracanthus tenellus (EECT) could improve immunomodulatory property of murine monocyte/macrophage RAW 264.7 cells. Methods: Cell viability, phagocytic ability, and nitric oxide were measured. The levels of prostaglandin E
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In this study, we investigated the inhibitory effect of 5-aminolevulinic acid (ALA), a heme precursor, on inflammatory and oxidative stress activated by lipopolysaccharide (LPS) in RAW 264.7 macrophages by estimating nitric oxide (NO), prostaglandin E2 (PGE2), cytokines, and reactive oxygen species (ROS). We also evaluated the molecular mechanisms through analysis of the expression of their regulatory genes, and further evaluated the anti-inflammatory and antioxidant efficacy of ALA against LPS in the zebrafish model. Our results indicated that ALA treatment significantly attenuated the LPS-induced release of pro-inflammatory mediators including NO and PGE2, which was associated with decreased inducible NO synthase and cyclooxygenase-2 expression. ALA also inhibited the LPS-induced expression of pro- inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6, reducing their extracellular secretion. Additionally, ALA abolished ROS generation, improved the mitochondrial mass, and enhanced the expression of heme oxygenase-1 (HO-1) and the activation of nuclear translocation of nuclear factor-E2-related factor 2 (Nrf2) in LPS-stimulated RAW 264.7 macrophages. However, zinc protoporphyrin, a specific inhibitor of HO-1, reversed the ALA-mediated inhibition of pro-inflammatory cytokines production and activation of mitochondrial function in LPS-treated RAW 264.7 macrophages. Furthermore, ALA significantly abolished the expression of LPS-induced pro-inflammatory mediators and cytokines, and showed strong protective effects against NO and ROS production in zebrafish larvae. In conclusion, our findings suggest that ALA exerts LPS-induced anti-inflammatory and antioxidant effects by upregulating the Nrf2/HO-1 signaling pathway, and that ALA can be a potential functional agent to prevent inflammatory and oxidative damage.
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Objective: To investigate whether the ethanol extract of Chondracanthus tenellus (Harvey) Hommersand, a type of red algae, could exhibit anti-inflammatory potential in lipopolysaccharide (LPS)-stimulated macrophages. Methods: The ethanol extract of Chondracanthus tenellus was applied to 100 ng/mL LPS-stimulated RAW 264.7 cells, and cell viability, phagocytic ability, levels of pro-inflammatory factors, and the production of reactive oxygen species were measured. To identify the underlying mechanism of the ethanol extract of Chondracanthus tenellus, the expression of inflammation-regulated genes was estimated. Results: The ethanol extract of Chondracanthus tenellus had no cytotoxic effect at concentrations below 300 μg/mL, and reduced the LPS-induced production of inflammatory mediators including nitric oxide (NO) and prostaglandin E 2. Furthermore, the extract markedly suppressed the expression of inducible NO synthase and cyclooxygenase-2, as well as the production of reactive oxygen species. The LPS-induced up-regulation of pro-inflammatory cytokines was attenuated by treatment with the ethanol extract of Chondracanthus tenellus, reducing their extracellular secretion. The Chondracanthus tenellus extract also inhibited LPS-mediated activation of nuclear factor-kappa B (NF-κB). In addition, the phosphorylation of mitogen activated protein kinases (MAPKs) and phosphatidylinositol 3 kinase (PI3K)/Akt was markedly increased by LPS, which was significantly abolished by the Chondracanthus tenellus extract. Conclusions: Our findings indicate that the ethanol extract of Chondracanthus tenellus exhibited potential anti-inflammatory and antioxidant effects through downregulating the NF-κB, MAPKs, and PI3K/Akt signaling pathways in LPS stimulated RAW 264.7 macrophages.
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Objective: To investigate whether ethanol extracts of Chondracanthus tenellus (EECT) could improve immunomodulatory property of murine monocyte/macrophage RAW 264.7 cells. Methods: Cell viability, phagocytic ability, and nitric oxide were measured. The levels of prostaglandin E
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Objective: To investigate whether ethanol extracts of Hizikia fusiforme could induce apoptosis in human prostate cancer PC3 cells.Methods: Cell viability was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide. Apoptosis and mitochondrial membrane potential (MMP) were measured using flow cytometry in PC3 cells. DNA damage was assessed by nuclear staining and DNA fragmentation assay. Expressions of apoptosis-associated proteins were determined by Western blotting assays. Activities of caspase-3, -8, and -9 were determined by colorimetric assay. Moreover, intracellular reactive oxygen species (ROS) generation was detected using a flow cytometer and fluorescence microscope. Results: Treatment of PC3 cells with ethanol extracts of Hizikia fusiforme inhibited proliferation, which was associated with induction of apoptosis, and accompanied by increased expression of Fas, Fas-ligand (FasL), Bax and tBid, and decreased expression of Bcl-2. In addition, ethanol extracts of Hizikia fusiforme reduced c-Flip expression and activated caspase-8, -9 and -3, resulting in an increase in poly (ADP-ribose) polymerase (PARP)cleavage. However, in the presence of a pan-caspase inhibitor, ethanol extracts of Hizikia fusiforme-mediated growth inhibition and apoptosis were significantly attenuated. Ethanol extracts of Hizikia fusiforme also destroyed the integrity of mitochondria due to the loss of MMP, leading to cytosolic release of cytochrome c. Moreover, the levels of ROS were markedly increased by treatment with ethanol extracts of Hizikia fusiforme, which was significantly suppressed by the ROS scavenger N-acetyl-L-cysteine. Further investigation of whether ethanol extracts of Hizikia fusiforme-induced apoptosis was related to the generation of ROS was conducted and the results showed that N-acetyl-L-cysteine fully blocked ethanol extracts of Hizikia fusiforme-induced apoptotic events including loss of MMP, activation of caspase-3, the cytosolic release of cytochrome c and cytotoxicity.Conclusions: Ethanol extracts of Hizikia fusiforme have chemopreventive potential via induction of ROS-dependent apoptosis. Therefore, ethanol extracts of Hizikia fusiforme may be useful for developing effective and selective natural sources to inhibit cancer cell proliferation.
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Background and Objectives@#To evaluate mismatches between pure-tone audiometry (PTA) and auditory steady-state response (ASSR) tests in non-auditory neuropathy adults and investigate brain lesions that may explain the mismatches, especially in cases where the ASSR threshold was worse than the estimated PTA threshold.Subjects and Method PTA, speech audiometry, auditory brainstem response, ASSR, and neuroimaging tests were carried out on individuals selected. Among them, medical records of 30 subjects (16 males, 14 females; mean age=54.4±13.2 years) with significant mismatches between PTA and estimated ASSR thresholds were analyzed retrospectively. All neuroimaging tests were reviewed to identify any neurologic abnormalities. @*Results@#Pathologic brain lesions were found in 19 cases (63.3%) in the study group, all of which showed significant mismatch in hearing threshold between PTA and ASSR. Seven case of ischemic brain lesions (23.3%), five tumorous lesions (16.6%), and four brain vessel anomalies (13.3%) were found. Brain hemorrhage due to trauma were found in two cases (6.6%) as well as one case (3.3%) of unruptured aneurysm. Central auditory pathway disorder was suspected in two cases. The 11 cases showing normal results in the imaging studies included one mental retardation, one brain concussion, and seven cases (23.3%) with no specific causes. Six tinnitus cases included two subjects showing discrepancies between frequency matching in the tinnitogram. @*Conclusion@#In adults with a mismatch between PTA thresholds and estimated ASSR thresholds, especially for those with moderate to profound hearing loss, additional neuroimaging tests and other audiologic tests may reveal other possible causes of hearing loss.
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The thioredoxin (Trx) system plays critical roles in regulating intracellular redox levels and defending organisms against oxidative stress. Recent studies indicated that Trx reductase (TrxR) was overexpressed in various types of human cancer cells indicating that the Trx-TrxR system may be a potential target for anti-cancer drug development. This study investigated the synergistic effect of auranofin, a TrxR-specific inhibitor, on sulforaphane-mediated apoptotic cell death using Hep3B cells. The results showed that sulforaphane significantly enhanced auranofin-induced apoptosis by inhibiting TrxR activity and cell proliferation compared to either single treatment. The synergistic effect of sulforaphane and auranofin on apoptosis was evidenced by an increased annexin-V-positive cells and Sub-G1 cells. The induction of apoptosis by the combined treatment caused the loss of mitochondrial membrane potential (ΔΨm) and upregulation of Bax. In addition, the proteolytic activities of caspases (-3, -8, and -9) and the degradation of poly (ADP-ribose) polymerase, a substrate protein of activated caspase-3, were also higher in the combined treatment. Moreover, combined treatment induced excessive generation of reactive oxygen species (ROS). However, treatment with N-acetyl-L-cysteine, a ROS scavenger, reduced combined treatment-induced ROS production and apoptosis. Thereby, these results deduce that ROS played a pivotal role in apoptosis induced by auranofin and sulforaphane. Furthermore, apoptosis induced by auranofin and sulforaphane was significantly increased through inhibition of the phosphoinositide 3-kinase (PI3K)/Akt pathway. Taken together, the present study demonstrated that down-regulation of TrxR activity contributed to the synergistic effect of auranofin and sulforaphane on apoptosis through ROS production and inhibition of PI3K/Akt signaling pathway.
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Objectives@#. Although osteotomy is an important part of rhinoplasty, it is known to be closely related to postoperative eyelid edema and ecchymosis. We aimed to evaluate the effects of periosteal elevation prior to osteotomy on eyelid edema and ecchymosis. @*Methods@#. Two authors reviewed studies in the Medline, Scopus, and Cochrane databases published through May 2019. Randomized controlled trials comparing periosteal elevation (subperiosteal tunneling) with periosteal preservation that reported eyelid edema or ecchymosis or subconjunctival hemorrhage as outcomes of interest were included. From each study, the baseline characteristics of the study subjects, the quality of the study, the number of patients in the treatment and control groups, and outcomes were extracted. @*Results@#. Data for meta-analysis were identified in six studies with a total of 208 patients. Eyelid ecchymosis and edema within 3 days postoperatively were significantly more common in the periosteal elevation group than in the preservation group, although such an association was not found for edema on postoperative day 7 (standardized mean difference [SMD], 0.21; 95% confidence interval [CI], –0.09 to 0.50; I2 =0%). There was no significant difference in subconjunctival hemorrhage on day 1 (SMD, 0.31; 95% CI, –0.09 to 0.72; I2 =0%). @*Conclusion@#. Periosteal preservation during lateral osteotomy may reduce eyelid edema and ecchymosis compared to periosteal elevation. Further studies with rigorous research methods should be carried out to determine the effectiveness of different techniques in lateral osteotomy.
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Objective: To investigate whether ethanol extracts of Hizikia fusiforme could induce apoptosis in human prostate cancer PC3 cells. Methods: Cell viability was evaluated using 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide. Apoptosis and mitochondrial membrane potential (MMP) were measured using flow cytometry in PC3 cells. DNA damage was assessed by nuclear staining and DNA fragmentation assay. Expressions of apoptosis-associated proteins were determined by Western blotting assays. Activities of caspase-3, -8, and -9 were determined by colorimetric assay. Moreover, intracellular reactive oxygen species (ROS) generation was detected using a flow cytometer and fluorescence microscope. Results: Treatment of PC3 cells with ethanol extracts of Hizikia fusiforme inhibited proliferation, which was associated with induction of apoptosis, and accompanied by increased expression of Fas, Fas-ligand (FasL), Bax and tBid, and decreased expression of Bcl-2. In addition, ethanol extracts of Hizikia fusiforme reduced c-Flip expression and activated caspase-8, -9 and -3, resulting in an increase in poly (ADP-ribose) polymerase (PARP)cleavage. However, in the presence of a pan-caspase inhibitor, ethanol extracts of Hizikia fusiforme-mediated growth inhibition and apoptosis were significantly attenuated. Ethanol extracts of Hizikia fusiforme also destroyed the integrity of mitochondria due to the loss of MMP, leading to cytosolic release of cytochrome c. Moreover, the levels of ROS were markedly increased by treatment with ethanol extracts of Hizikia fusiforme, which was significantly suppressed by the ROS scavenger N-acetyl-L-cysteine. Further investigation of whether ethanol extracts of Hizikia fusiforme-induced apoptosis was related to the generation of ROS was conducted and the results showed that N-acetyl-L-cysteine fully blocked ethanol extracts of Hizikia fusiforme-induced apoptotic events including loss of MMP, activation of caspase-3, the cytosolic release of cytochrome c and cytotoxicity. Conclusions: Ethanol extracts of Hizikia fusiforme have chemopreventive potential via induction of ROS-dependent apoptosis. Therefore, ethanol extracts of Hizikia fusiforme may be useful for developing effective and selective natural sources to inhibit cancer cell proliferation.
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Background@#A nationwide outbreak of foot-and-mouth disease (FMD) in South Korea caused massive economic losses in 2010. Since then, the Animal and Plant Quarantine Agency (QIA) has enhanced disinfection systems regarding livestock to prevent horizontal transmission of FMD and Avian influenza (AI). Although the amount of disinfectant used continues to increase, cases of FMD and AI have been occurring annually in Korea, except 2012 and 2013. @*Objectives@#This study measured the concentration of the disinfectant to determine why it failed to remove the horizontal transmission despite increased disinfectant use. @*Methods@#Surveys were conducted from February to May 2017, collecting 348 samples from disinfection systems. The samples were analyzed using the Standards of Animal Health Products analysis methods from QIA. @*Results@#Twenty-three facilities used inappropriate or non-approved disinfectants. Nearly all sampled livestock farms and facilities—93.9%—did not properly adjust the disinfectant concentration. The percentage using low concentrations, or where no effective substance was detected, was 46.9%. Furthermore, 13 samples from the official disinfection station did not use effective disinfectant, and—among 72 samples from the disinfection station—88.89% were considered inappropriate concentration, according to the foot-and-mouth disease virus guidelines; considering the AIV guideline, 73.61% were inappropriate concentrations. Inappropriate concentration samples on automatic (90.00%) and semi-automatic (90.90%) disinfection systems showed no significant difference from manual methods (88.24%). Despite this study being conducted during the crisis level, most disinfectants were used inappropriately. @*Conclusions@#This may partially explain why horizontal transmission of FMD and AI cannot be effectively prevented despite extensive disinfectant use.
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Niño , Humanos , Resistencia de las Vías Respiratorias , Cefalometría , Hidrocortisona , Hueso Hioides , Métodos , Apnea Obstructiva del Sueño , Columna VertebralRESUMEN
BACKGROUND: A pharmacist's participation in medical rounds in intensive care unit (ICU) is becoming popular nowadays. In this study, we investigated the effect of pharmacologic intervention by a pharmacist's participation in medical round in ICU on prevention of adverse drug events (ADEs). METHODS: From March 2011 to July 2011, the intervention data were obtained by participating in medical round two or three times a week, and by reviewing electronic medical records of patients admitted to surgical ICU. The incidence, cause, and type of ADEs were noted, respectively. Expected cost avoidance was calculated from interventions, which were considered to be preventive of ADEs. The acceptance rate of pharmacologic interventions was noted. RESULTS: Among 2781 patients, a total of 159 intervention data were collected in 90 patients. Recommendation for drug dosage adjustment or monitoring in patients with potential overdose and sub-therapeutic dose made up 82% of the total interventions. In 8% of interventions, initiation of drug therapy was recommended. 83% of the interventions were accepted and the acceptance rate of interventions within 24 hrs was 58%. The rate of the interventions, which were considered to be preventive of ADEs was 62%. Expected cost reduction obtained by preventing ADEs was 25,867,083 Won during a 5-month period. CONCLUSIONS: A pharmacist's participation in physician rounds in ICU was associated with prevention of ADEs and subsequent reduction of the cost in drug therapy.