In this study, we found that alpha-pinene (α-pinene) exhibits anti-inflammatory activity through the suppression of mitogen-activated protein kinases (MAPKs) and the nuclear factor-kappa B (NF-κB) pathway in mouse peritoneal macrophages. α-Pinene is found in the oils of many coniferous trees and rosemary. We investigated the inhibitory effects of α-Pinene on inflammatory responses induced by lipopolysaccharide (LPS) using mouse peritoneal macrophages. α-Pinene significantly decreased the LPS-induced production of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and nitric oxide (NO). α-Pinene also inhibited inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expressions in LPS-stimulated macrophages. Additionally, the activations of MAPKs and NF-κB were attenuated by means of α-pinene treatment. These results indicate that α-pinene has an anti-inflammatory effect and that it is a potential candidate as a new drug to treat various inflammatory diseases.
Vanillic acid is a benzoic acid derivative that is used as a flavoring agent. It is an oxidized form of vanillin. At present, the mechanisms by which vanillic acid exerts its anti-inflammatory effects are incompletely understood. In this study, we attempted to determine the effects of vanillic acid on lipopolysaccharide (LPS)-induced inflammatory responses in mouse peritoneal macrophages. Our findings indicate that vanillic acid inhibits LPS-induced production of tumor necrosis factor (TNF)-α and interleukin (IL)-6. During the inflammatory process, the levels of cyclooxygenase (COX)-2 and nitric oxide (NO) increased in mouse peritoneal macrophages, but vanillic acid suppressed both the enhanced levels of COX-2 and the production of prostaglandin E(2) and NO. Moreover, vanillic acid suppressed the activation of nuclear factor-kappa B (NF-κB) and caspase-1. These results provide novel insights into the pharmacological actions of vanillic acid and are indicative of the potential use of this molecule in the treatment of inflammatory diseases.
We herein investigated the role of the STAT signaling cascade in the production of pro-inflammatory cytokines and cisplatin ototoxicity. A significant hearing impairment caused by cisplatin injection was observed in Balb/c (wild type, WT) and STAT4 −/− , but not in STAT6 −/− mice. Moreover, the expression levels of the protein and mRNA of proinflammatory cytokines, including TNF-α, IL-1β, and IL-6, were markedly increased in the serum and cochlea of WT and STAT4 −/− , but not STAT6 −/− mice. Organotypic culture revealed that the shape of stereocilia bundles and arrays of sensory hair cell layers in the organ of Corti from STAT6 −/− mice were intact after treatment with cisplatin, whereas those from WT and STAT4 −/− mice were highly distorted and disarrayed after the treatment. Cisplatin induced the phosphorylation of STAT6 in HEI-OC1 auditory cells, and the knockdown of STAT6 by STAT6-specific siRNA significantly protected HEI-OC1 auditory cells from cisplatin-induced cell death and inhibited pro-inflammatory cytokine production. We further demonstrated that IL-4 and IL-13 induced by cisplatin modulated the phosphorylation of STAT6 by binding with IL-4 receptor alpha and IL-13Rα1. These findings suggest that STAT6 signaling plays a pivotal role in cisplatin-mediated pro-inflammatory cytokine production and ototoxicity.
The development of complex products, such as automobiles, involves engineering changes that frequently require redesigning or altering the products. Although it has been found that efficient management of knowledge and collaboration in engineering changes is crucial for the success of new product development, extant systems for engineering changes focus mainly on storing documents related to the engineering changes or simply automating the approval processes, while the knowledge that is generated from collaboration and decision-making processes may not be captured and managed easily. This consequently limits the use of the systems by the participants in engineering change processes. This paper describes a model for knowledge management and collaboration in engineering change processes, and based on the model, builds a prototype system that demonstrates the model's strengths. We studied a major Korean automobile company to analyze the automobile industry's unique requirements regarding engineering changes. We also developed domain ontologies from the case to facilitate knowledge sharing in the design process. For achieving efficient retrieval and reuse of past engineering changes, we used a case-based reasoning (CBR) with a concept-based similarity measure.
Software processes must be properly designed according to various project characteristics, past experiences, and improvement initiatives in order to ensure the quality of software products. Because various types of knowledge are required for designing software processes, many parts of the designs depend on the knowledge of experts and manual activities. Consequently, design processes can be time-consuming and error prone. To overcome this problem, this paper proposes a mechanism that supports the customization of software processes. Since integration of various types of knowledge is required in the customization process, the proposed approach uses a hybrid method combining CBR (Case Based Reasoning) and knowledge-based technique. CBR is used to facilitate re-use of past experiences; knowledge-based technique is used to derive process components using knowledge-based inferencing and to resolve conflicts that may occur during customization. To support the two approaches in a seamless manner, an organizational process library (PL) is designed which defines and shares various types of process knowledge and reusable objects throughout the whole customization procedure. An illustrative example is presented to show how the hybrid approach can be used to design actual software processes.
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