Near-infrared-responsive GE11-CuS@Gal nanoparticles as an intelligent drug release system for targeting therapy against oral squamous cell carcinoma.

Galangin (Gal) is a natural plant flavonoid. More and more evidence shows that Gal can achieve anti-tumor effects by regulating various mechanisms. However, its poor water solubility, low bioavailability, and insufficient lesion targeting limit its clinical application. To overcome these shortcomings, we designed and developed a mesoporous nanosystem (GE11-CuS) that actively located the target area and photo-controlled drug release, which promoted the rapid accumulation of drugs in tumor tissues under NIR irradiation, thus achieving positive effects against cancer. In this study, we explored the application of the Gal-loaded nanometer system (GE11-CuS@Gal) in the treatment of oral squamous cell carcinoma (OSCC) both in vitro and in vivo. The results exhibited that GE11-CuS@Gal had excellent targeting ability and could accumulate efficiently in tumor cells (HSC-3). Meanwhile, the temperature of GE11-CuS@Gal increasing rapidly under NIR illumination damaged the integrity of the carrier and allowed Gal molecules to escape from the pores of the nanoparticles. When the accumulation of Gal in the nidus reached a certain level, the intracellular ROS level could be significantly increased and the antioxidative stress pathway mediated by Nrf2/OH-1 was effectively blocked, to inhibit the growth and migration of tumors. In conclusion, the GE11-CuS improved the antitumor activity of Gal in the body, which laid a foundation for the treatment of OSCC with traditional Chinese medicine ingredients.

Dietary flavonoids: a novel strategy for the amelioration of cognitive impairment through intestinal microbiota.

The chances of people suffering from cognitive impairments increase gradually with age. Diet and lifestyle are closely related to the occurrence and development of cognitive function. Dietary flavonoid supplementation has been shown to be one of the protective factors against cognitive decline. Flavonoids belong to a class of polyphenols that have been proposed for the treatment of cognitive decline. Recent evidence has shown that intestinal flora in the human body can interact with flavonoids. Intestinal microbiota can modify the chemical structure of flavonoids, producing new metabolites, the pharmacological activities of which may be different from those of the parent; meanwhile, flavonoids and their metabolites can, in turn, regulate the composition and structure of intestinal flora. Notably, intestinal flora affect host nervous system activity through the gut-brain axis, ultimately causing changes in cognitive function. This review therefore summarizes the interaction of dietary flavonoids and intestinal flora, and their protective effect against cognitive decline through the gut-brain axis, indicating that dietary flavonoids may ameliorate cognitive impairment through their interaction with intestinal microbiota. © 2022 Society of Chemical Industry.

A nomogram to predict hyperkalemia in patients with hemodialysis: a retrospective cohort study.

BACKGROUND: Hyperkalemia increases the risk of mortality and cardiovascular-related hospitalizations in patients with hemodialysis. Predictors of hyperkalemia are yet to be identified. We aimed at developing a nomogram able to predict hyperkalemia in patients with hemodialysis. METHODS: We retrospectively screened patients with end-stage renal disease (ESRD) who had regularly received hemodialysis between Jan 1, 2017, and Aug 31, 2021, at Lishui municipal central hospital in China. The outcome for the nomogram was hyperkalemia, defined as serum potassium [K+] ≥ 5.5 mmol/L. Data were collected from hemodialysis management system. Least Absolute Shrinkage Selection Operator (LASSO) analysis selected predictors preliminarily. A prediction model was constructed by multivariate logistic regression and presented as a nomogram. The performance of nomogram was measured by the receiver operating characteristic (ROC) curve, calibration diagram, and decision curve analysis (DCA). This model was validated internally by calculating the performance on a validation cohort. RESULTS: A total of 401 patients were enrolled in this study. 159 (39.65%) patients were hyperkalemia. All participants were divided into development (n = 256) and validation (n = 145) cohorts randomly. Predictors in this nomogram were the number of hemodialysis session, blood urea nitrogen (BUN), serum sodium, serum calcium, serum phosphorus, and diabetes. The ROC curve of the training set was 0.82 (95%CI 0.77, 0.88). Similar ROC curve was achieved at validation set 0.81 (0.74, 0.88). The calibration curve demonstrated that the prediction outcome was correlated with the observed outcome. CONCLUSION: This nomogram helps clinicians in predicting the risk of PEW and managing serum potassium in the patients with hemodialysis.

Understanding the paradox between tragedies of the commons and the anticommons: From a cognitive psychology perspective.

The tragedy of the commons refers to the overuse of resources which are rival in consumption but lack excludability and it also refers to rent dissipation. While the tragedy of the anticommons is a tragedy closely connected with underuse of resources that are rival in consumption and with too strong excludability. The prior studies proved that the tragedy of the commons and the tragedy of the anticommons are symmetric from the perspective of pure mathematics, especially the game theory, which was later refuted by behavioral economics experiments. According to them, the tragedy of the anticommons is severer than the tragedy of the commons. The asymmetry of the tragedy of the commons and the tragedy of the anticommons is a paradox by these different research methods. This paradox shows that there are imperfections in the completely rational economic man hypothesis set up by neoclassical economics. As a fundamental theory, the tragedy of the commons is quite influential in many disciplines, such as microeconomics, public sector economics, ecological economics, environmental economics, management, sociology, property law, and political science. And the tragedy of the anticommons theory has also opened its door of both theoretical research and practical implications since its acceptance by Nobel laureate Buchanan, the main founder of public choice school. Only when theoretical issues are thoroughly discussed and made clear enough, can people avoid misunderstanding or misusing the commons theory. Thus, it is necessary to elucidate the paradox between them. Based on Simon's bounded rationality, Kahneman and Tversky's prospect theory, value function, Thaler's mental accounting, endowment effect, and other cognitive psychological tools, this study clearly shows that agents' decision-making process is not just based on the long-believed marginal benefit and marginal cost analysis advocated by traditional neoclassical economists. Agents' decision-making is a process in which agents selectively absorb, code the objective marginal revenue and marginal cost, and feed relevant information to their brain. Therefore, what plays a directly decisive role is not the objective marginal revenue and marginal cost per se, but the mentally perceived subjective utility of marginal revenue and marginal cost by the human brain. Followed by this research clue, the paradox between the tragedy of the commons and the tragedy of the anticommons is elucidated from the perspective of cognitive psychology.

Comparative efficacy of intravenous and oral iron supplements for the treatment of iron deficiency in patients with heart failure: A network meta-analysis of randomized controlled trials.

OBJECTIVE: We aimed at comparing the efficacy of intravenous and oral iron supplementations for the treatment of iron deficiency (ID) in patients with heart failure (HF). METHODS: We searched the PubMed, Cochrane, and Embase databases from inception to January 15, 2022. We included randomized controlled trials enrolling patients with HF who were treated for ID with intravenous iron supplements, oral iron supplements, or placebo. The primary outcomes were all-cause death, cardiovascular mortality, and hospitalization for heart failure. The secondary outcomes were evaluated through the six-minute walking test (6MWT) and the Kansas City Cardiomyopathy Questionnaire (KCCQ). RESULTS: The network meta-analysis included sixteen studies. Compared to placebo/control groups, intravenous iron supplements did not decrease all-cause death (0.69, 0.39-1.23) or cardiovascular mortality (0.89, 0.66-1.20). After 12 weeks, a reduced hospitalization for heart failure was associated with the administration of intravenous iron supplementations (0.58, 0.34-0.97). The most significant improvements regarding 6MWT (44.44, 6.10-82.79) and KCCQ (5.96, 3.19-8.73) were observed with intravenous iron supplements. Oral iron supplements reduced hospitalization for heart failure (0.36, 0.14-0.96) and all-cause death (0.34, 0.12-0.95), but did not influence the 6MWT (29.74, -47.36 to 106.83) and KCCQ (0.10, -10.95 to 11.15). CONCLUSIONS: Administering intravenous iron supplements for ID in patients with HF improves their exercise capacity and quality of life. In order to reduce hospitalizations for heart failure, the supplementation should be administered for more than 12 weeks. Although oral iron supplements did not improve exercise capacity and quality of life, they could reduce all-cause death and hospitalizations for heart failure.

Case Report: Torsade de Pointes Induced by the Third-Generation Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor Osimertinib Combined With Litsea Cubeba.

Torsades de Pointes (TdP) occurred in a 68-year-old female with epidermal growth factor receptor (EGFR) mutant lung cancer administered osimertinib, the third-generation EGFR tyrosine kinase inhibitor (TKI). Electrocardiogram (ECG) recorded at Tdp showed QT prolongation (QTc = 515 ms), to which a Traditional Chinese Medicine (TCM) named "Litsea Cubeba" may have contributed. After discontinuation of osimertinib and Litsea Cubeba, magnesium supplementation, potassium supplementation, lidocaine infusion, and the pacemaker frequency adjustment, Tdp terminated. However, QT prolongation sustained at discharge (QTc = 528 ms), partly because of the emergency use of amiodarone. Osimertinib may prolong the QT interval leading to TdP, especially when multiple risk factors to lengthen QT interval are incidentally overlapped. Thus, regular monitoring of ECG and appropriate management of concomitant drugs are highly recommended.

Plant Polysaccharides Modulate Immune Function via the Gut Microbiome and May Have Potential in COVID-19 Therapy.

Plant polysaccharides can increase the number and variety of beneficial bacteria in the gut and produce a variety of active substances, including short-chain fatty acids (SCFAs). Gut microbes and their specific metabolites have the effects of promoting anti-inflammatory activity, enhancing the intestinal barrier, and activating and regulating immune cells, which are beneficial for improving immunity. A strong immune system reduces inflammation caused by external viruses and other pathogens. Coronavirus disease 2019 (COVID-19) is still spreading globally, and patients with COVID-19 often have intestinal disease and weakened immune systems. This article mainly evaluates how polysaccharides in plants can improve the immune system barrier by improving the intestinal microecological balance, which may have potential in the prevention and treatment of COVID-19.

Efficacy of brain natriuretic peptide vs. nicorandil in preventing contrast-induced nephropathy: a network meta-analysis.

This study aimed to conduct a network meta-analysis (NMA) to compare the efficacy of brain natriuretic peptide (BNP) vs nicorandil for preventing contrast-induced nephropathy (CIN). Databases of Pubmed, Cochrane, Embase, Web of Science were searched by keywords for eligible studies of randomized controlled trials investigating different agents (BNP, nicorandil, nitroglycerin, intravenous saline) for preventing CIN. The outcomes included a change in serum creatinine level at 48 h and the incidence of CIN after percutaneous coronary intervention (PCI) or coronary angiography (CAG). A total of 13 studies with 3,462 patients were included. Compared with intravenous saline alone, except for nitroglycerin (odds ratio [OR]: 1.02, 95% CI [0.36-2.88]), the other drugs significantly reduced the CIN incidence with OR of 0.35 (95% CI [0.24-0.51]) for BNP, 0.52 (0.29, 0.94) for usual-dose nicorandil, 0.28 (0.19, 0.43) for double-dose nicorandil. BNP and double-dose nicorandil significantly decreased the change of serum creatinine (SCr) levels with mean difference (MD) of -6.98, (-10.01, -3.95) for BNP, -8.78, (-11.63, -5.93) for double-dose nicorandil. No significant differences were observed in the change of SCr levels for nitroglycerin (-4.97, [-11.46, 1.52]) and usual-dose nicorandil (-2.32, [-5.52, 0.89]) compared with intravenous saline alone. For double-dose nicorandil, the CIN incidence and the change of SCr level in group of 4-5 days treatment course were more than group of less than or equal to 24 h treatment course (OR of 1.48, [0.63-3.46] and MD of 2.48, [-1.96, 6.91]). In conclusion, BNP and double-dose nicorandil can have effects on preventing the incidence of CIN and double-dose nicorandil performed better than BNP. In double-dose nicorandil groups, a course of less than or equal to 24 h before and after procedure performed with better efficacy than a course of 4-5 days.

Preparation and antitumor activity of bFGF-mediated active targeting doxorubicin microbubbles.

Characterization and antitumor activity of basic fibroblast growth factor-mediated active targeting doxorubicin microbubbles (bFGF-DOX-MB) were investigated. Pluronic F68 with chemical conjugation of doxorubicin (DOX-P) and peptide KRTGQYKLC-conjugated DSPE-PEG2000 were prepared. bFGF-DOX-MB had a normal distribution of particle size, with average particle size of 2.7 µm. Using A549 mouse model, bFGF-DOX-MB combined ultrasound showed the best inhibition effect on tumor volume growth among all the test groups. Similar conclusion was obtained from experimental measurements of tumor weight change and blood cell count. From the results, chemotherapeutic drug inhibition on tumor growth could be enhanced by local ultrasound combined with active targeting bFGF-DOX-MB, which might provide a potential application for ultrasound-mediated chemotherapy.