In the past few decades, intracellular calcium overload has been shown to induce cell death through multiple signaling pathways. In this study, we used BAPTA-AM, a well-known membrane-permeable Ca2+ chelator, to prevent cell injury by allaying the intracellular calcium overload. We explored the clinical potentials of BAPTA-AM-loaded liposome (BAL) in the treatment of the acute liver failure (ALF) mouse model, which is characterized by severe hepatic necrosis and apoptosis. We discovered that BAL can significantly inhibit D-GalN-induced LO2 cell damage as it increased cell viability by 60% and downregulated the LPS-stimulated inflammatory response in RAW 264.7 macrophages by reversing the morphological change and modulating TNF-α and NF-κB expressions. Through systemic administration, BAL can rapidly accumulate in damaged liver tissue and exhibit excellent treatment effects on the D-GalN/LPS-induced ALF mouse model, including elevation of the survival rate (from 10 to 80%), recovery of normal liver indexes and liver health indicators, improvement of liver blood microcirculation (increased the blood flow volume by 80% and flow rate by 60%), and blood coagulation. The underlying hepatoprotective effect of BAL is presumably based on the antinecrosis and antiapoptosis abilities attributed to its inhibition on oxidative stress, restriction on TNF-α receptor, and mitochondria-mediated apoptotic pathway by effectively clearing the overloaded intercellular calcium. BAL holds great potential as a new therapeutic strategy for ALF treatment, and its prominent cell rescue ability provides ample opportunities for the treatment of many other diseases that are characterized by rapid and massive cell damage.
Background. Abelmoschus manihot (L.) Medic flower is a medicinal plant for the treatment of diseases in China. e present study was carried out to scientifically validate the gastroprotective activity and clarify the possible mechanism of the total flavones from Abelmoschus manihot (L.) Medic flowers (TFA). Methods. Gastric ulcer was induced in mice by oral administration of ethanol. e gastroprotective activity of TFA was evaluated by the gastric ulcer index and histological examinations. e gastric tissue was collected in the form of homogenate. e level of malondialdehyde (MDA) and glutathione (GSH), the activity of superoxide dismutase (SOD), and protein content were measured. Western blotting for the expression of Bax, Bcl-2, TNF-α, and NF-κB(p65) was also carried out. e effect of TFA was compared with that of standard antiulcer drug omeprazole (100 mg/kg). Results. is gastroprotective effect of TFA could be attributed to the increase in the activity of SOD and GSH and decrease in the levels of MDA and also decrease in the levels of Bax, TNF-α, and NF-κB(p65) expressions and increase in the Bcl-2 expression level. Conclusion.e findings of this study demonstrated that TFA could significantly attenuate ethanol-induced gastric injury via antioxidative, anti-inflammatory, and antiapoptotic effects.
ObjectiveTo explore the clinical efficacy and adverse reactions of Jiawei Maxing Shigan Tang (JMST; a modified decoction of ephedra, apricot kernel, gypsum, and licorice) combined with western medicine in the symptomatic treatment of COVID-19.MethodsIn this study, we retrospectively collected the basic data of 48 patients with COVID-19 who were discharged from our hospital between January 20 and February 28, 2020. Besides, the blood routines, biochemical indexes, nucleic acid detection results, clinical symptoms, lung imaging improvements, adverse reactions, and other clinical data of these patients before and after treatment were recorded. Finally, we drew comparisons between the outcomes and adverse reactions of patients in the combined treatment group (therapeutic regimen recommended by authoritative guidelines and supplemented by JMST) and the conventional treatment group (therapeutic regimen recommended by authoritative guidelines).ResultsThere were no significant differences in age, gender, clinical classification, and underlying medical conditions between the combined treatment group (28 cases) and the conventional treatment group (20 cases). However, the combined treatment group presented superior results to the conventional treatment group in several key areas. For instance, patients produced negative nasal/throat swab-based nucleic acid detection results in a shorter time, clinical symptoms were more effectively alleviated, and the absorption time of lung exudation was shorter (P < 0.05). Furthermore, the combined treatment group had a shorter length of stay (LOS) and faster lymphocyte recovery duration than the conventional treatment group, although the differences were not statistically significant. Moreover, there were no significant differences concerning gastrointestinal reaction, hepatic injury, renal impairment, myocardial injury, and other adverse reactions between the two groups.ConclusionThe results of this study indicate that JMST combined with the recommended therapeutic regimen enhances the recovery of COVID-19 patients without increasing the risk of adverse reactions. Therefore, this therapy promotes positive outcomes for COVID-19 patients.
Nanoparticle delivery systems have been shown to improve the therapeutic efficacy of anti-cancer drugs, including a variety of drugs for the treatment of hepatocellular carcinoma (HCC). However, the current systems show some limitations, and the delivery of more effective nanoparticle systems for anti-HCC drugs with better targeting ability are needed. Here, we created paclitaxel (PTX)/norcantharidin (NCTD)-loaded core–shell lipid nanoparticles modified with a tumor neovasculature-targeted peptide (Ala-Pro-Arg-Pro-Gly, APRPG) and investigated their anti-tumor effects in HCC. Core–shell-type lipid nanoparticles (PTX/NCTD-APRPG-NPs) were established by combining poly(lactic-co-glycolic acid) (PLGA)-wrapped PTX with phospholipid-wrapped NCTD, followed by modification with APRPG. For comparison, PTX-loaded PLGA nanoparticles (PTX-NPs) and PTX/NCTD-loaded core–shell-type nanoparticles without APRPG (PTX/NCTD-NPs) were prepared. The in vitro and in vivo anti-tumor effects were examined in HepG2 cells and tumor-bearing mice, respectively. Morphological and release characterization showed that PTX/NCTD-APRPG-NPs were prepared successfully and achieved up to 90% release of PTX in a sustained manner. Compared with PTX/NCTD-NPs, PTX/NCTD-APRPG-NPs significantly enhanced the uptake of PTX. Notably, the inhibition of proliferation and migration of hepatoma cells was significantly higher in the PTX/NCTD-APRPG-NP group than those in the PTX-NP and PTX/NCTD-NP groups, which reflected significantly greater anti-tumor properties as well. Furthermore, key molecules in cell proliferation and apoptosis signaling pathways were altered most in the PTX/NCTD-APRPG-NP group, compared with the PTX-NP and PTX/NCTD-NP groups. Collectively, PTX/NCTD-loaded core–shell lipid nanoparticles modified with APRPG enhance the effectiveness of anti-HCC drugs and may be an effective system for the delivery of anti-HCC drugs.
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