These results indicate that SKI 306X inhibited PG degradation in cartilage explant culture, and its prophylactic administration significantly protected the knee joint of rabbit from OA-like change in collagenase-induced experimental OA model. This strongly suggests that SKI 306X can be a good OA agent with some cartilage protection activity.

Abstract. SKI306X was previously found to have cartilage protective effects in the experimental osteoarthritis (OA) model. To investigate the chondro-protective benefits of SKI306X for its capacity in altering changes in cartilage metabolism and molecular mechanisms of cartilage protective action, SKI306X is studied in rabbit cartilage explants culture. To investigate the protective effect of SKI306X on cartilage catabolism, we assessed collagen degradation in rabbit cartilage explants treated with interleukin-1α up to 3 weeks. To examine the reaction mechanism, matrix metalloproteinase (MMPs) were investigated by fluorimetric and Western blotting analysis. In addition, its effects on the activation process of proenzyme MMP-3 were determined by gelatin zymography. SKI306X significantly inhibited collagen degradation and inhibited the activities of several MMPs. Total MMPs activities in cultured medium were substantially increased in the third week at the time of collagen degradation with the absence of SKI306. However, the introduction of SKI306X decreased MMPs activities in cultured medium. Furthermore, Western blotting analysis proved that these inhibitory effects of this drug were the result of inhibiting MMPs expression. SKI306X also inhibited the activation of proenzyme MMP-3 to the active form of MMP-3. These results indicate that SKI306X inhibits matrix degradation by down regulating MMPs expression and secretion, inhibition of MMPs activity, and inhibiting activation of MMP-3 during the collagen breakdown process.

Electrochemical CO2 reduction (ECO2R) is considered as one of economically viable means to convert CO2 into useful products, for achieving carbon neutrality in the future. Many studies have been conducted...

Microalgae is a promising biomass source for renewable fuels and chemicals production. To describe microalgal behavior and improve their cultivation, various kinetic models have been proposed. However, previous works have focused on biomass formation and lipids production only, even though carbohydrates and proteins are also important products, not only for understanding the metabolic behavior of microalgae but also for enhancing the economic viability through value-added side products. In this study, a new mathematical model is proposed to explain core biological mechanisms of growth and macromolecules syntheses based on the central metabolism of carbon and nitrogen. In the model, microalgal growth is separated as hyperplasia and hypertrophy, to describe the cell growth more precisely under nutrient-replete and -deplete conditions. Sensitivity analysis performed using the model indicates that cell state (e.g., cell death rate) has a strong effect on the lipid production explaining the difficulty of reproducing a microalgae culture experiment.

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SKI306X was previously reported to have good anti-inflammatory and analgesic efficacy in various studies. To determine its mode of action, an investigation was carried out for some representative mediators. Arachidonic acid metabolism and its products are particularly important in inflammation and pain. The pro-inflammatory cytokines, especially interleukin-1 (IL-1) and tumor necrosis factor (TNF-a a), and induced nitric oxide (NO) appear to be most involved in the inflammatory process such as osteoarthritis (OA). Thus SKI306X was tested to determine the effects on enzymes related to arachidonic acid metabolism and the release or synthesis of inflammatory mediators. SKI306X did inhibit the expression of cyclooxygenase-2 (COX-2) enzyme without affecting COX-1 and COX-2 activity. Leukotriene B 4 (LTB 4 ) production also was inhibited by SKI306X (IC 50 ‫62.4؎7.89؍‬ m mg/ml). SKI306X inhibited significantly TNF-a a release (IC 50 ‫8.71؎6.79؍‬ m mg/ml) and NO production (IC 50 ‫؍‬ 280؎17.8 m mg/ml). But IL-1a a release was not attenuated by SKI306X. This study suggests that inhibition of these mediators by SKI306X may be one of the mechanisms responsible for its anti-inflammatory effects.

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