Objective. To investigate the molecular mechanisms of the antiarthritic effects of bee venom (BV) and melittin (a major component of BV) in a murine macrophage cell line (Raw 264.7) and in synoviocytes obtained from patients with rheumatoid arthritis.Methods. We evaluated the antiarthritic effects of BV in a rat model of carrageenan-induced acute edema in the paw and in a rat model of chronic adjuvantinduced arthritis. The inhibitory effects of BV and melittin on inflammatory gene expression were measured by Western blotting, and the generation of prostaglandin E 2 (PGE 2 ) and nitric oxide (NO) and the intracellular calcium level were assayed. NF-B DNA binding and transcriptional activity were determined by gel mobility shift assay or by luciferase assay. Direct binding of BV and melittin to the p50 subunit of NF-B was determined with a surface plasmon resonance analyzer.Results. BV (0.8 and 1.6 g/kg) reduced the effects of carrageenan-and adjuvant-induced arthritis. This reducing effect was consistent with the inhibitory effects of BV (0.5, 1, and 5 g/ml) and melittin (5 and Conclusion. Target inactivation of NF-B by directly binding to the p50 subunit is an important mechanism of the antiarthritic effects of BV.
Acute kidney injury (AKI) is a frequent complication of liver transplantation and is associated with increased mortality. We identified the incidence and modifiable risk factors for AKI after living-donor liver transplantation (LDLT) and constructed risk scoring models for AKI prediction. We retrospectively reviewed 538 cases of LDLT. Multivariate logistic regression analysis was used to evaluate risk factors for the prediction of AKI as defined by the RIFLE criteria (RIFLE = risk, injury, failure, loss, end stage). Three risk scoring models were developed in the retrospective cohort by including all variables that were significant in univariate analysis, or variables that were significant in multivariate analysis by backward or forward stepwise variable selection. The risk models were validated by way of cross-validation. The incidence of AKI was 27.3% (147/538) and 6.3% (34/538) required postoperative renal replacement therapy. Independent risk factors for AKI by multivariate analysis of forward stepwise variable selection included: body-mass index >27.5 kg/m2 [odds ratio (OR) 2.46, 95% confidence interval (CI) 1.32–4.55], serum albumin <3.5 mg/dl (OR 1.76, 95%CI 1.05–2.94), MELD (model for end-stage liver disease) score >20 (OR 2.01, 95%CI 1.17–3.44), operation time >600 min (OR 1.81, 95%CI 1.07–3.06), warm ischemic time >40 min (OR 2.61, 95%CI 1.55–4.38), postreperfusion syndrome (OR 2.96, 95%CI 1.55–4.38), mean blood glucose during the day of surgery >150 mg/dl (OR 1.66, 95%CI 1.01–2.70), cryoprecipitate > 6 units (OR 4.96, 95%CI 2.84–8.64), blood loss/body weight >60 ml/kg (OR 4.05, 95%CI 2.28–7.21), and calcineurin inhibitor use without combined mycophenolate mofetil (OR 1.87, 95%CI 1.14–3.06). Our risk models performed better than did a previously reported score by Utsumi et al. in our study cohort. Doses of calcineurin inhibitor should be reduced by combined use of mycophenolate mofetil to decrease postoperative AKI. Prospective randomized trials are required to address whether artificial modification of hypoalbuminemia, hyperglycemia and postreperfusion syndrome would decrease postoperative AKI in LDLT.
Chimeric antigen receptor‐T (CAR‐T) cell immunotherapy has shown impressive clinical outcomes for hematologic malignancies. However, its broader applications are challenged due to its complex ex vivo cell‐manufacturing procedures and low therapeutic efficacy against solid tumors. The limited therapeutic effects are partially due to limited CAR‐T cell infiltration to solid tumors and inactivation of CAR‐T cells by the immunosuppressive tumor microenvironment. Here, a facile approach is presented to in vivo program macrophages, which can intrinsically penetrate solid tumors, into CAR‐M1 macrophages displaying enhanced cancer‐directed phagocytosis and anti‐tumor activity. In vivo injected nanocomplexes of macrophage‐targeting nanocarriers and CAR‐interferon‐γ‐encoding plasmid DNA induce CAR‐M1 macrophages that are capable of CAR‐mediated cancer phagocytosis, anti‐tumor immunomodulation, and inhibition of solid tumor growth. Together, this study describes an off‐the‐shelf CAR‐macrophage therapy that is effective for solid tumors and avoids the complex and costly processes of ex vivo CAR‐cell manufacturing.
This study focuses on perceived value, which is not mentioned in previous internet-only bank studies, to analyze the popularity of internet-only banks. It does this by exploring the relationships between the perceived value and usage intention of customers. The purpose of this study is to help us understand customers’ decision making to accept innovative services by finding factors that affect consumer acceptance of internet-only banks. Using multiple regression, this study analyzes data gathered from college students in their 20s who are familiar with IT services and are interested in internet-only banks. The results show that all three components of perceived value (economical value, convenience value, and emotional value) increase usage intention. Convenience value is the most important factor in the acceptance of internet-only banking services. The findings indicate that perceived value is an attractive factor in using internet-only banks and suggest that managing and developing perceived value is an important marketing strategy.
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