崇城大学

Pirarubicin (THP) is a potent anthracycline anticancer agent; however, its clinical use is limited by nonselective tissue distribution and systemic toxicity. This study aimed to evaluate whether palmitic acid-modified THP nanoparticles (Pal-THP nanoparticles) could improve the in vivo therapeutic profile of THP. Pal-THP nanoparticles stabilized by albumin as a formulation stabilizer were prepared by antisolvent precipitation. Antitumor efficacy, biodistribution, and drug forms (intact Pal-THP and the free THP released from Pal-THP) were evaluated in colon 26 tumor-bearing mice following intravenous administration. Acute systemic and hemolytic toxicity were assessed relative to THP. Pal-THP nanoparticles significantly suppressed tumor growth compared with the control group, without inducing body weight loss, whereas THP exhibited a tendency toward tumor suppression but did not reach statistical significance versus control at an equivalent dose. While the absolute tumor accumulation of Pal-THP nanoparticles was limited, it was significantly higher than that of THP. Importantly, there was efficient conversion of Pal-THP to free THP in tumor tissue, which is consistent with the presence of an acid‑labile hydrazone linkage. Pal-THP nanoparticles also markedly attenuated acute systemic and hemolytic toxicity, in contrast to THP, under the present experimental conditions. Pal-THP nanoparticles altered the in vivo fate of THP through tumor accumulation and tumor-localized conversion to free THP. This resulted in effective tumor suppression and a significant reduction in toxicity compared to THP in mice. Thus, this formulation strategy represents a promising approach for improving the therapeutic index of chemotherapy using THP and other anthracyclines.

This study deals with the feasibility of active temperature control with a pulsating flow for various industrial applications such as thermal devices and many kinds of manufacturing for further improvements of their performance and product quality. The authors focus on the heat-transfer characteristics on the flat plate installed in a pulsating duct flow. Experiments aiming to make clear the effect of flow conditions (time-averaged flow rate, pulsating frequency and amplitude) on heattransfer in pulsating flows with two different flow-rate fluctuation modes (continuous sinusoidal wave and intermittent pulse wave) have been conducted. In the past experiments, regardless of pulsation mode, no difference in heat-transfer between steady flow and pulsating flow was obtained when flow was supplied with uniform velocity distribution at the inlet. Heat-transfer enhancement by flow pulsation was confirmed when flow was supplied with non-uniform velocity distribution at the inlet, regardless of pulsation mode. This tendency was confirmed in both flow regimes of laminar and turbulent flows. To elucidate the mechanisms of such heat-transfer enhancement especially for the laminar flow regime in cases with non-uniform inflow conditions, local velocity measurements of its temporal fluctuation and time-averaged value in the channel-width direction were carried out with a hot-wire anemometer. Measurements were conducted for four cross sections in the flow direction. The results showed that the time-averaged velocity profile changed along with the flow direction from a non-uniform to a uniform one. This tendency was observed more clearly with increasing pulsating frequency.

One of the most important goals in aerospace engineering applications is the creation of new "flyable" systems. In a flight demonstration using the sounding rocket S-520-34, we show the first successful operation of a bipropellant cylindrical rotating detonation engine using liquid ethanol and liquid nitrous oxide, Detonation Engine System 2 (DES2), in a space environment. From the pressure and temperature histories, the combustion was finished before all propellants were consumed because nitrogen was supplied earlier than the ideal depletion time due to spin stabilization of the sounding rocket. Therefore, the combustion pressure decreased from the nitrogen-supply start time. The short-time Fourier transform result indicated that the deflagration mode, two-wave mode, and single-wave mode occurred in sequence. This was attributed to the locally lower liquid temperatures, wall temperature, and mixture ratio at ignition near the wall, where the rotating detonation wave propagated. A comparison of the filling mass and consumption indicated that the mass flow rate estimated using control surface theory reflects an actual phenomenon. As for the propulsive performance, the experimental characteristic exhaust velocity was almost the same as the ideal value. Moreover, a specific impulse efficiency of more than 90% was achieved throughout the rotating detonation engine operation.

Acetaminophen (APAP) is a widely used antipyretic and analgesic agent; however, overdose can lead to hepatotoxicity and, in severe cases, acute liver failure. Development of therapeutics that mitigate APAP-induced liver injury is essential to prevent progression to hepatic failure. Upon overdose, APAP is metabolized in the liver to the highly reactive electrophile N-acetyl-p-benzoquinone imine (NAPQI), which induces hepatocellular damage. Glutathione (GSH), a key intracellular nucleophile, exists partially in a modified form as glutathione hydropersulfide (GSSH), which exhibits enhanced nucleophilicity and functions as a supersulfide. While detoxification of NAPQI via GSH conjugation is well established, the role of GSSH in NAPQI detoxification has remained unknown. In this study, we investigated the protective role of hepatic supersulfides against APAP-induced liver injury using a murine model. Utilizing a newly developed tandem mass spectrometry technique, we demonstrated that supersulfides form conjugates with NAPQI, which are subsequently excreted in the urine. Moreover, administration of supersulfide donors, such as N-acetylcysteine (NAC) tetrasulfide and thioglucose tetrasulfide, elevated hepatic supersulfide levels and significantly attenuated APAP-induced liver injury. Notably, the protective effects of these donors surpassed those of conventional NAC treatment. Our findings suggest that the hepatoprotective effects of supersulfide donors involve not only enhanced detoxification of NAPQI, thereby reducing hepatocellular damage, but also suppression of inflammation. These results highlight the therapeutic potential of targeting hepatic supersulfides in the treatment of APAP overdose.

Pirarubicin nanoparticles were prepared using the amphiphilic protein hydrophobin with a particle size of 84.13 ± 2.23 nm as a carrier. Furthermore, glucosamine was incorporated into the formulation to develop glucosamine-containing pirarubicin hydrophobin nanoparticles with a particle size of 111.41 ± 3.62 nm. The anticancer effects of the nanoparticles were evaluated in C26 cells and tumor-bearing mice, compared with pirarubicin alone. The evaluation in C26 cells revealed that nanoparticles with added glucosamine exhibited significantly more vigorous anticancer activity than nanoparticles alone. Moreover, glucosamine nanoparticles demonstrated a considerably higher tumor-site antitumor effect in tumor-bearing mice than nanoparticles and pirarubicin. These results suggest that glucosamine-containing pirarubicin hydrophobin nanoparticles are highly efficient and selective, holding promise for future clinical applications.