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The methanolic extract of the fruits of Cornus officinalis S et Z. (Cornaceae) showed the significant neuroprotective activity against glutamate-induced toxicity in HT22 hippocampal cells. Chemical profile of n-BuOH fraction of the methanolic extract of C. officinalis fruits, which showed the most potent activity, was established using HPLC-diode array detector-electrospray-MS (HPLC-DAD-ESI-MS). Through bioactivity-guided isolation, five iridoid glycosides including one new compound, 7-O-butylmorroniside (1), loganin (2), morroniside (3), 7R-O-methylmorroniside (4), 7S-O-methylmorroniside (5) were isolated from the n-BuOH fraction. The protective activities of the isolated compounds, themselves, were not statistically significant. However, the hydrolyzed products of compounds 1, 4 and 5 significantly protected glutamate-injured HT22 cells up to 78±2.2%, 60±3.2% and 59±2.5% of non-treated control, respectively. [ABSTRACT FROM AUTHOR]

Background. We investigated the efficacy of a 3C protease inhibitor (3CPI) in a murine coxsackievirus B3 (CVB3) myocarditis model. CVB3 is a primary cause of viral myocarditis. The CVB3 genome encodes a single polyprotein that undergoes a series of proteolytic events to produce several viral proteins. Most of this proteolysis is catalyzed by the 3C protease (3CP). Methods and Results. By way of a micro-osmotic pump, each mouse received 50 mM 3CPI in 100 [mu]L of 100% dimethyl sulfoxide (DMSO) during a 72-hour period. On the day of pump implantation, mice (n = 40) were infected intraperitoneally with 10(6) plaque-forming units of CVB3. For the infected controls (n = 50), the pump was filled with 100% DMSO without 3CPI. The 3-week survival rate of 3CPI-treated mice was significantly higher than that of controls (90% vs 22%; P < .01). Myocardial inflammation, viral titers, and viral RNA levels were also reduced significantly in the 3CPI-treated group compared with these measures in the controls. Conclusions. The protein-based drug 3CPI inhibited the activity of 3CP of CVB3, significantly inhibited viral proliferation, and attenuated myocardial inflammations, subsequent fibrosis, and CVB3-induced mortality in vivo. Thus, this CVB3 3CPI has the potential to be a novel therapeutic agent for the treatment of acute viral myocarditis during the viremic phase. [ABSTRACT FROM AUTHOR]

Bakuchicin is a furanocoumarin derived from the seeds of Psoralea corylifolia. The aim of the present study was to investigate the effect of bakuchicin on vascular tone in rat aortic tissue. Bakuchicin induced a dose-dependent relaxation of phenylephrine-precontracted rat aorta which was abolished by removal of the endothelium. Pretreatment of the endothelium-intact aortic tissues with NG-nitro- l-arginine methylester (L-NAME) or 1H-[1,2,4]-oxadiazole-[4,3-[alpha]]-quinoxalin-1-one (ODQ) significantly inhibited the vascular relaxation induced by bakuchicin. Incubation with bakuchicin increased the production of cGMP in a concentration-dependent manner, and this effect was blocked by pretreatment with both L-NAME and ODQ. Vascular relaxation induced by bakuchicin was significantly inhibited by pretreatment with verapamil and diltiazem, but not by several other inhibitors including tetraethylammonium (TEA), glibenclamide, indomethacin, atropine or propranolol. These results suggested that bakuchicin-induced vasodilatation is closely associated with the endothelium-dependent nitric oxide (NO)/cGMP signaling pathway, with the possible involvement of L-type Ca(2+) channels. Copyright © 2011 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The principal objective of the present study was to evaluate the antimetastatic activity of decursin and decursinol isolated from Angelica gigas. Decursin and decursinol inhibited the proliferation and invasion of CT-26 colon carcinoma cells. The expressions of matrix metalloproteinase (MMP)-2 and MMP-9 in cells and the activities in the culture medium were also reduced by decursin and decursinol treatment. In CT-26 cells, the extracellular signal-regulated kinase (ERK) inhibitor inhibited cell proliferation, invasion and MMP-9 expression, and the c-Jun N-terminal kinase (JNK) inhibitor suppressed the expression of both MMPs, as well as cell proliferation and cell invasion. The phosphatidylinositol-3 kinase (PI3K) inhibitor reduced only the expression of MMP-2. In addition, the invasion of CT-26 cells was inhibited by the treatment with anti-MMP-9 antibody, rather than anti-MMP-2 antibody. These results indicate that MMP-9 expression via ERK and JNK plays a critical role for the invasion of CT26 cells. Decursin and decursinol downregulated ERK and JNK phosphorylation. Moreover, oral administration of decursin and decursinol reduced the formation of tumor nodules in the lungs and the increase in lung weight caused by CT-26 metastases. Therefore, both decursin and decursinol may be beneficial antimetastatic agents, targeting MMPs and their upstream signaling molecules. [ABSTRACT FROM AUTHOR]

The n-BuOH fraction of O. javanica significantly protected the primary cultures of rat cortical cells exposed to glutamate. Four flavonoids yielded from this fraction through bioactivity-guidance. The isolated compounds, identified as isorhamnetin (1), afzelin (2), hyperoside (3) and persicarin (4), were evaluated in vitro for their neuroprotective activity. Persicarin (4), the main constituent of O. javanica, showed significant neuroprotective activities in glutamate-injured rat cortical cells. Persicarin diminished calcium influx and inhibited the subsequent overproduction of nitric oxide and intracellular peroxide. In addition, persicarin significantly restored the reduced activities of glutathione (GSH) reductase and glutathione peroxidase, and the contents of GSH induced by glutamate. These results support a conclusion that persicarin greatly contributes to the neuroprotective activities of O. javanica. [ABSTRACT FROM AUTHOR]

Oral Diseases (2010) 16, 375–381 Objective: Porphyromonas gingivalis can invade and survive within its host epithelial cells. The aim of this study was to test our hypothesis that persistent presence of intracellular periodontal pathogens in gingival tissue causes the chronic inflammation and that an inappropriate immune response is a risk factor for periodontitis. Methods: Together with the presence of P. gingivalis, the distribution of B cells, plasma cells, and CD4+, CD8+, and FOXP3+ regulatory T cells was evaluated in gingival tissues from healthy ( n = 7) and periodontitis ( n = 8) sites by in situ hybridization and immunohistochemistry, respectively. Results: Porphyromonas gingivalis was detected in proximity to inflammatory infiltrates in three and seven biopsies from the healthy and periodontitis sites, respectively. Compared with healthy sites, periodontal lesions contained a significantly increased number of each immune cell studied with a relative dominance of plasma cells over T cells. Conclusions: Persistent bacterial invasion of gingival tissues in combination with a plasma cell-dominant immune response may be involved in the pathogenesis of periodontitis. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate the long-term outcomes of endovascular treatment of central venous stenosis in patients with arteriovenous fistulas (AVFs) for hemodialysis. Five hundred sixty-three patients with AVFs who were referred for a fistulogram were enrolled in this study. Among them, 44 patients showed stenosis (n = 35) or occlusions (n = 9) in the central vein. For the initial treatment, 26 patients underwent percutaneous transluminal angioplasty (PTA) and 15 patients underwent stent placements. Periods between AVF formation and first intervention ranged from 3 to 144 months. Each patient was followed for 14 to 60 months. Procedures were successful in 41 of 44 patients (93.2%). Primary patency rates for PTA at 12 and 36 months were 52.1% and 20.0%, and assisted primary patency rates were 77.8% and 33.3%, respectively. Primary patency rates for stent at 12 and 36 months were 46.7% and 6.7%, and assisted primary patency rates were 60.0% and 20.0%, respectively. Fifteen of 26 patients with PTAs underwent repeated interventions because of restenosis. Fourteen of 15 patients with a stent underwent repeated interventions because of restenosis and combined migration (n = 1) and shortening (n = 6) of the first stent. There was no significant difference in patency between PTAs and stent placement (p > 0.05). Average AVF patency duration was 61.8 months and average number of endovascular treatments was 2.12. In conclusion, endovascular treatments of central venous stenosis could lengthen the available period of AVFs. There was no significant difference in patency between PTAs and stent placement. [ABSTRACT FROM AUTHOR]

The extract of Angelicae Dahuricae Radix has traditionally been used as an anti-noceptive remedy in China. In this study, the methanol extract of Angelicae Dahuricae Radix (MEAD) was evaluated to determine if it has anti-noceptive and anti-inflammatory action. The anti-nociceptive activities of MEAD were evaluated by determining the writhing response and sleeping time, as well as by a formalin test. In addition, the anti-inflammatory activities of MEAD were evaluated by a vascular permeability test as well as by measuring the carrageenan-induced paw edema and conducting a myeloperoxidase (MPO) assay. MEAD (600 and 1200mg/kg) exhibited anti-inflammatory effects on acetic acid-induced vascular permeability, carrageenan-induced paw edema, and MPO activity. Moreover, the results of the formalin test, the acetic acid-induced writhing response and the pentobarbital-induced sleeping time indicated that MEAD had anti-nociceptive effects that occurred in a concentration dependent manner. To determine the mechanism by which MEAD exerted its effects on the expression of inducible nitric oxide synthase (iNOS) and the production of nitric oxide (NO) by treated murine macrophage RAW 264.7 cells was evaluated. Similar to the in vivo activities, both the iNOS expression and NO production were significantly suppressed by MEAD in a dose-dependent manner. Furthermore, MEAD inhibited the activating phosphorylation of ERK1/2. These results provide a scientific basis that explains the mechanism by which Angelicae Dahuricae Radix relieves inflammatory pain. [ABSTRACT FROM AUTHOR]

Investigates the long-term equity performance of Japanese firms issuing convertible debt and equity. Performance of firms issuing public convertible debt; Contrast with security-issuing firms in the United States; Underreaction hypothesis; Implications for the long-term performance of the issuing firms in light of evidence from the U.S.; Relation between announcement returns and long-term returns.

Background: Three-phase bone scintigraphy (TPBS) is an established objective diagnostic method for complex regional pain syndrome (CRPS), but its validity remains controversial. The aims of this study were: (i) to re-evaluate the diagnostic performance of TPBS, and (ii) to suggest new TPBS criteria based on the proposed research criteria for CPRS in Budapest (the 2003 Budapest research criteria).Methods: The medical records of 228 consecutive patients, evaluated using the Budapest research criteria, were retrospectively analysed. Of these, 116 patients were included in the present study, and 69 of 116 were diagnosed to have CRPS based on these criteria. The diagnostic performance of TPBS was assessed by determining its sensitivity, specificity, and positive and negative likelihood ratios, and new criteria for TPBS were identified by pattern analysis using the Budapest research criteria.Results: The sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of TPBS for the diagnosis of CRPS according to the Budapest research criteria were 40.0, 76.5, 1.73, and 0.78, respectively. Furthermore, D-D-D, D-D-S, and D-D-I patterns [i.e. according to decreased (D), symmetrical (S), or increased (I) tracer uptake during Phases I, II, and III] of TPBS were found to be positively predictive for CRPS.Conclusions: The diagnostic value of a positive TPBS for CRPS is low from the view point of the Budapest research criteria. Our findings suggest that a diagnosis of CRPS using the Budapest research criteria should be considered when decreased patterns of TPBS are observed during Phases I and II. [ABSTRACT FROM AUTHOR]

The interaction of estrogen with the estrogen receptor (ER, principally ERalpha) induces growth of human breast tumor cells. In contrast, ERalpha-positive cells have been described as non-dividing cells in normal breast (though estrogen stimulation of ERalpha cells directs the division of neighboring cells). However, there is a small sub-population of cells in normal mammary tissue that are ERalpha-positive, that can divide, and therefore share this property with human breast tumor cells. In order to investigate their pattern of growth regulation, we measured the fraction of dividing ERalpha(+) cells during normal growth and compared that to glands stimulated by oncogenic Wnt effectors. First, we found there was no difference between the rate of division of ERalpha(+) cells and ERalpha(-) cells, whether the population was responding to estrogen or Wnt mitogens. The proportion of dividing ERalpha(+) mammary epithelial cells was increased (10x) in response to pregnancy, and similar increases were observed in response to ectopic Wnt signaling. We propose that Wnt signaling can substitute for estrogen to drive total population growth (that includes ERalpha(+) cells). Although the E-ERalpha-derived mitogenic response is situated in a minority of the luminal cells, and the Wnt-LRP5/6-derived mitogenic response is situated in a minority of basal cells, overall, the growth response of the mammary epithelial population is remarkably similar. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study was to investigate the predictive factors for persistent disease activity following anti-vascular endothelial growth factors (anti-VEGF) and their long-term effects in patients to be treated for neovascular age-related macular degeneration (nAMD) under real-world conditions., Methods: Retrospective data analysis of the PROOF study, a multi-center real-world retrospective chart review conducted across Korea in patients with nAMD included treatment-naive patients with nAMD who received first anti-VEGF (ranibizumab, bevacizumab, or aflibercept) between January 2017 and March 2019 was performed. All 600 patients (cohort 1) had a minimum follow-up of 12 months of which 453 patients (cohort 2) were followed-up for 24 months from baseline., Results: At month 12 after anti-VEGF therapy, 58.10% (95% confidence interval [CI]: 54.09, 62.12) of patients and at month 24, 66.02% of patients continued to have persistent retinal fluid. At both months 12 and 24, predictive factors for persistent disease activity were fibrovascular pigment epithelial detachments (PED) (P = 0.0494) and retinal fluid at month 3 after loading phase (P = 0.0082). The mean changes in visual acuity were + 6.2, + 10.1, and + 13.3 letters and in the central subfield thickness were - 79.1 µm, - 96.3 µm, and - 134.4 µm at 12 months from baseline, in the bevacizumab, aflibercept, and ranibizumab groups, respectively., Conclusions: The presence of retinal fluid after loading phase and fibrovascular PED were predictors of persistent disease activity after at least 1 year of anti-VEGF treatment., (© 2024. The Author(s).)

Liposomes are applied to various anticancer treatments as representative drug delivery carriers. However, liposomes do not have their own targeting properties; therefore, there are limitations in drug delivery to specific tissues or cells. High targetability in drug delivery is an important factor in improving bioavailability and drug efficacy and reducing side effects; recent research has been actively investigated to modify the surface of liposomes to give them specific functions. In this study, we studied a drug delivery system for anticancer treatment that enhances targeting ability through fusion with exosomes on the surface of liposomes. We designed exosome-liposome hybrid nanoparticles loaded with a gemcitabine prodrug as a treatment for pancreatic ductal adenocarcinoma (PDAC). Membrane fusion with exosomes shows excellent targeting ability to pancreatic cancer cells due to intrinsic targeting ability and expansion of the macropinocytosis pathway.

Background: Glycopeptides for ampicillin-susceptible Enterococcus faecalis/faecium bacteremia are readily prescribed depending on the severity of the condition. However, there is limited data on the outcomes of glycopeptide use compared to ampicillin-containing regimens for ampicillin-susceptible E. faecalis/faecium bacteremia. From an antibiotic stewardship perspective, it is important to determine whether the use of glycopeptides is associated with improved clinical outcomes in patients with ampicillin-susceptible E. faecalis/faecium bacteremia., Methods: This retrospective cohort study was conducted at a university-affiliated hospital between January 2010 and September 2019. We collected data from patients with positive blood cultures for Enterococcus species isolates. The clinical data of patients who received ampicillin-containing regimens or glycopeptides as definitive therapy for ampicillin-susceptible E. faecalis/faecium bacteremia were reviewed. Multivariate logistic regression analysis was performed to identify risk factors for 28-day mortality., Results: Ampicillin-susceptible E. faecalis/faecium accounted for 41.2% (557/1,353) of enterococcal bacteremia cases during the study period. A total of 127 patients who received ampicillin-containing regimens (N = 56) or glycopeptides (N = 71) as definitive therapy were included in the analysis. The 28-day mortality rate was higher in patients treated with glycopeptides (19.7%) than in those treated with ampicillin-containing regimens (3.6%) (p = 0.006). However, in the multivariate model, antibiotic choice was not an independent predictor of 28-day mortality (adjusted OR, 3.7; 95% CI, 0.6-23.6)., Conclusions: Glycopeptide use was not associated with improved mortality in patients with ampicillin-susceptible E. faecalis/faecium bacteremia. This study provides insights to reduce the inappropriate use of glycopeptides in ampicillin-susceptible E. faecalis/faecium bacteremia treatment and promote antimicrobial stewardship., (© 2024. The Author(s).)

The emerging field of gut-lung axis research has revealed a complex interplay between the gut microbiota and respiratory health, particularly in asthma. This review comprehensively explored the intricate relationship between these two systems, focusing on their influence on immune responses, inflammation, and the pathogenesis of respiratory diseases. Recent studies have demonstrated that gut microbiota dysbiosis can contribute to asthma onset and exacerbation, prompting investigations into therapeutic strategies to correct this imbalance. Probiotics and prebiotics, known for their ability to modulate gut microbial compositions, were discussed as potential interventions to restore immune homeostasis. The impact of antibiotics and metabolites, including short-chain fatty acids produced by the gut microbiota, on immune regulation was examined. Fecal microbiota transplantation has shown promise in various diseases, but its role in respiratory disorders is not established. Innovative approaches, including mucus transplants, inhaled probiotics, and microencapsulation strategies, have been proposed as novel therapeutic avenues. Despite challenges, including the sophisticated adaptability of microbial communities and the need for mechanistic clarity, the potential for microbiota-based interventions is considerable. Collaboration between researchers, clinicians, and other experts is essential to unravel the complexities of the gut-lung axis, paving a way for innovative strategies that could transform the management of respiratory diseases.