Dual Drug-Loaded Nanoliposomes Encapsulating Curcumin and 5-Fluorouracil with Advanced Medicinal Applications: Self-Monitoring and Antitumor Therapy.

Due to the presence of physiological barriers, it is difficult to achieve the desired therapeutic efficacy of drugs; thus, it is necessary to develop an efficient drug delivery system that enables advanced functions such as self-monitoring. Curcumin (CUR) is a naturally functional polyphenol whose effectiveness is limited by poor solubility and low bioavailability, and its natural fluorescent properties are often overlooked. Therefore, we aimed to improve the antitumor activity and drug uptake monitoring by simultaneously delivering CUR and 5-Fluorouracil (5-FU) in the form of liposomes. In this study, dual drug-loaded liposomes (FC-DP-Lip) encapsulating CUR and 5-FU were prepared by the thin-film hydration method; their physicochemical properties were characterized; and their biosafety, drug uptake distribution in vivo, and tumor cell toxicity were evaluated. The results showed that the nanoliposome FC-DP-Lip showed good morphology, stability, and drug encapsulation efficiency. It showed good biocompatibility, with no side effects on zebrafish embryonic development. In vivo uptake in zebrafish showed that FC-DP-Lip has a long circulation time and presents gastrointestinal accumulation. In addition, FC-DP-Lip was cytotoxic against a variety of cancer cells. This work showed that FC-DP-Lip nanoliposomes can enhance the toxicity of 5-FU to cancer cells, demonstrating safety and efficiency, and enabling real-time self-monitoring functions.

Nano-Liposomes Double Loaded with Curcumin and Tetrandrine: Preparation, Characterization, Hepatotoxicity and Anti-Tumor Effects.

(1) Background: Curcumin (CUR) and tetrandrine (TET) are natural compounds with various bioactivities, but have problems with low solubility, stability, and absorption rate, resulting in low bioavailability, and limited applications in food, medicine, and other fields. It is very important to improve the solubility while maintaining the high activity of drugs. Liposomes are micro-vesicles synthesized from cholesterol and lecithin. With high biocompatibility and biodegradability, liposomes can significantly improve drug solubility, efficacy, and bioavailability. (2) Methods: In this work, CUR and TET were encapsulated with nano-liposomes and g DSPE-MPEG 2000 (DP)was added as a stabilizer to achieve better physicochemical properties, biosafety, and anti-tumor effects. (3) Results: The nano-liposome (CT-DP-Lip) showed stable particle size (under 100 nm) under different conditions, high solubility, drug encapsulation efficiency (EE), loading capacity (LC), release rate in vitro, and stability. In addition, in vivo studies demonstrated CT-DP-Lip had no significant toxicity on zebrafish. Tumor cytotoxicity test showed that CT-DP-Lip had a strong inhibitory effect on a variety of cancer cells. (4) Conclusions: This work showed that nano-liposomes can significantly improve the physical and chemical properties of CUR and TET and make them safer and more efficient.

Understanding the effects of pressure on the contact angle of water on a silicon surface in nitrogen gas environment: Contrasts between low- and high-temperature regimes.

HYPOTHESIS: Pressure dependence of contact angle is expected to be influenced by temperature. Nevertheless, the correlation of water contact angle with pressure is rarely investigated at high temperatures (over 100 ℃). EXPERIMENTS: In this work, measurements of the contact angle and interfacial tension of water in N2 atmosphere were conducted at various pressures and temperatures (up to 17 MPa and 300 ℃). The experimental observations were elucidated based on the theory of surface thermodynamics. FINDINGS: It was shown that the water-N2 interfacial tension linearly decreases with increasing the pressure, and that the pressure coefficient declines as temperature rises. The pressure dependence of the water contact angle was found to be different for the low- and high-temperature regimes: the water contact angle increases below 100 ℃, whereas an inverse variation occurs over 100 ℃. According to the theoretical analysis, the pressure dependence of both the water interfacial tension and contact angle is attributed to N2 adsorption on the surfaces of water and silicon. The variations in the water contact angle with pressure, including both the sign and magnitude, are actually the consequence of the changes of water-N2 and Si-N2 interfacial tensions manipulated by pressure and temperature.

Evaporation Kinetics of Sessile Water Droplets on a Smooth Stainless Steel Surface at Elevated Temperatures and Pressures.

The evaporation of water droplets on a solid surface at elevated temperatures under a pressurized condition has not yet been well understood, although this phenomenon is of both theoretical and practical significance. In this work, water droplet evaporation on smooth stainless steel surfaces in nitrogen gas atmosphere at elevated pressures and temperatures (up to 2 MPa and 202.4 °C, respectively) was investigated experimentally. It was observed that the increase in pressure diminishes the proportion of the constant contact radius stage over the entire evaporation time, whereas an opposite trend was found when raising the temperature, due to the change in the surface pinning ability with pressure (and temperature). The results also suggested that the evaporation mode transition is mainly affected by temperature rather than pressure. In addition, the evaporation rate was calculated under various degrees of subcooling, revealing that the evaporation rate increases almost linearly with pressure when keeping the degree of subcooling constant. However, when fixing the test temperature, a nonlinear decrease of the evaporation rate with pressure was observed. A power law growth of the evaporation rate with temperature was also found at a constant pressure. Last, it was uncovered by a theoretical analysis that the saturated vapor concentration is the dominant factor dictating the evaporation rate.

Applications, phytochemistry, pharmacological effects, pharmacokinetics, toxicity of Scutellaria baicalensis Georgi. and its probably potential therapeutic effects on COVID-19: a review.

Scutellaria baicalensis Georgi. (SB) is a common heat-clearing medicine in traditional Chinese medicine (TCM). It has been used for thousands of years in China and its neighboring countries. Clinically, it is mostly used to treat diseases such as cold and cough. SB has different harvesting periods and processed products for different clinical symptoms. Botanical researches proved that SB included in the Chinese Pharmacopoeia (1st, 2020) was consistent with the medicinal SB described in ancient books. Modern phytochemical analysis had found that SB contains hundreds of active ingredients, of which flavonoids are its major components. These chemical components are the material basis for SB to exert pharmacological effects. Pharmacological studies had shown that SB has a wide range of pharmacological activities such as antiinflammatory, antibacterial, antiviral, anticancer, liver protection, etc. The active ingredients of SB were mostly distributed in liver and kidney, and couldn't be absorbed into brain via oral absorption. SB's toxicity was mostly manifested in liver fibrosis and allergic reactions, mainly caused by baicalin. The non-medicinal application prospects of SB were broad, such as antibacterial plastics, UV-resistant silk, animal feed, etc. In response to the Coronavirus Disease In 2019 (COVID-19), based on the network pharmacology research, SB's active ingredients may have potential therapeutic effects, such as baicalin and baicalein. Therefore, the exact therapeutic effects are still need to be determined in clinical trials. SB has been reviewed in the past 2 years, but the content of these articles were not comprehensive and accurate. In view of the above, we made a comprehensive overview of the research progress of SB, and expect to provide ideas for the follow-up study of SB.

Vitamin B6 inhibits macrophage activation to prevent lipopolysaccharide-induced acute pneumonia in mice.

Macrophage activation participates in the pathogenesis of pulmonary inflammation. As a coenzyme, vitamin B6 (VitB6) is mainly involved in the metabolism of amino acids, nucleic acids, glycogen and lipids. We have previously reported that activation of AMP-activated protein kinase (AMPK) produces anti-inflammatory effects both in vitro and in vivo. Whether VitB6 via AMPK activation prevents pulmonary inflammation remains unknown. The model of acute pneumonia was induced by injecting mice with lipopolysaccharide (LPS). The inflammation was determined by measuring the levels of interleukin-1 beta (IL-1ß), IL-6 and tumour necrosis factor alpha (TNF-α) using real time PCR, ELISA and immunohistochemistry. Exposure of cultured primary macrophages to VitB6 increased AMP-activated protein kinase (AMPK) Thr172 phosphorylation in a time/dose-dependent manner, which was inhibited by compound C. VitB6 downregulated the inflammatory gene expressions including IL-1ß, IL-6 and TNF-α in macrophages challenged with LPS. These effects of VitB6 were mirrored by AMPK activator 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR). However, VitB6 was unable to inhibit LPS-induced macrophage activation if AMPK was in deficient through siRNA-mediated approaches. Further, the anti-inflammatory effects produced by VitB6 or AICAR in LPS-treated macrophages were abolished in DOK3 gene knockout (DOK3-/- ) macrophages, but were enhanced in macrophages if DOK3 was overexpressed. In vivo studies indicated that administration of VitB6 remarkably inhibited LPS-induced both systemic inflammation and acute pneumonia in wild-type mice, but not in DOK3-/- mice. VitB6 prevents LPS-induced acute pulmonary inflammation in mice via the inhibition of macrophage activation.

Impact of Perioperative Levosimendan Administration on Risk of Bleeding After Cardiac Surgery: A Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Levosimendan, a calcium sensitizer and potassium channel opener, has been demonstrated to improve myocardial function without increasing oxygen consumption and to show protective effects in other organs. Recently, a prospective, randomized controlled trial (RCT) revealed an association between levosimendan use and a possible increased risk of bleeding postoperatively. Levosimendan's anti-platelet effects have been shown in in vitro studies. Current studies do not provide sufficient data to support a relation between perioperative levosimendan administration and increased bleeding risk. PURPOSE: Our goal was to investigate the relation between perioperative levosimendan administration and increased bleeding risk using a meta-analysis study design. METHODS: The PubMed, Ovid, EMBASE and Cochrane Library databases were searched for relevant RCTs before July 1, 2019. The outcome parameters included reoperation secondary to increased bleeding in the postoperative period, the amount of postoperative recorded blood loss, and the need for transfusion of packed red blood cells (RBCs) and other blood products. RESULTS: A total of 1160 patients in nine RCTs (576 in the levosimendan group and 584 in the control group) were included according to our inclusion criteria. Analysis showed that perioperative levosimendan administration neither increased the rate of reoperation secondary to bleeding nor increased the amount of postoperative chest tube drainage when compared with the control group. In terms of blood product transfusion, levosimendan did not influence the requirement for RBC transfusion, platelet transfusion nor fresh frozen plasma (FFP) transfusion. Levosimendan also did not shorten or prolong the aortic cross-clamp time or the cardiopulmonary bypass time. CONCLUSION: The analyzed parameters, including reoperations due to bleeding, postoperative chest drainage and the requirement for blood products, revealed that levosimendan did not increase postoperative bleeding risk. More studies with a larger sample size are needed to address a more reliable conclusion due to study limitations.

Temperature dependence of contact angles of water on a stainless steel surface at elevated temperatures and pressures: In situ characterization and thermodynamic analysis.

Phase change heat transfer (e.g., boiling of water) on surfaces can be enhanced by tuning the surface wettability, which is often quantified by the contact angle and is expected to be influenced by temperature and pressure. However, the temperature (and pressure) dependence of contact angles of water on metallic surfaces remain unclear. In this study, an in situ characterization of the contact angles of water on 304 stainless steel surfaces at temperatures from room temperature to 250 °C and at pressures up to 15 MPa was performed using the sessile drop method. It was shown that three distinct regimes can be identified on the contact angle-temperature curves. A slightly-decreasing trend of the contact angles with temperature was observed below 120 °C, followed by a steeper linear decrease at higher temperatures. A further rise of the decreasing rate with temperature was observed above 210 °C. In contrast to temperature, the pressure was shown to have little effects on the contact angles. Based on the theory of surface thermodynamics, the effects of temperature (and pressure) on the contact angles were analyzed in terms of the interfacial tensions. An empirical correlation was developed to predict the contact angles as a function of temperature.