Echinocandins and triazoles were proven to be effective antifungal drugs against invasive fungal infections (IFI), which may cause significant morbidity and mortality in immunocompromised patients. The aim of this study was to compare the efficacy and safety between echinocandins and triazoles for the prophylaxis and treatment of fungal infections. PubMed, Embase, and the Cochrane Library were searched to identify relevant randomized controlled trials (RCTs) up to July 2014. The quality of trials was assessed with the Jadad scoring system. The primary outcomes of interest were treatment success, microbiological success, breakthrough infection, drug-related adverse events (AEs), withdrawals due to AEs, and all-cause mortality. Ten RCTs, involving 2,837 patients, were included, as follows: caspofungin versus fluconazole (n = 1), caspofungin versus itraconazole (n = 1), anidulafungin versus fluconazole (n = 1), micafungin versus fluconazole (n = 4), micafungin versus voriconazole (n = 2), and micafungin versus itraconazole (n = 1). Echinocandins and triazoles showed similar effects in terms of favorable treatment success rate [relative risk (RR) = 1.02, 95 % confidence interval (CI), 0.97–1.08], microbiological success rate (RR = 0.98, 95 % CI, 0.90–1.15), breakthrough infection (RR = 1.09; 95 % CI, 0.59–2.01), drug-related AEs (RR = 0.94; 95 % CI, 0.71–1.15), and all-cause mortality (RR = 0.85; 95 % CI, 0.66–1.10) in the prophylaxis and treatment of fungal infections. Additionally, echinocandins were more effective than triazoles for prophylaxis in patients undergoing hematologic malignancies or those who received hematopoietic stem cell transplantation (HSCT; RR = 1.08; 95 % CI, 1.02–1.15). Echinocandins significantly decreased the AE-related withdrawals rate compared with triazoles (RR = 0.47; 95 % CI, 0.33–0.67). This meta-analysis revealed that echinocandins are as effective and safe as triazoles for the prophylaxis and treatment of patients with fungal infections.
Myocardial infarction (MI) is caused by the formation of plaques in the arterial walls, leading to a decrease of blood flow to the heart and myocardium injury due to hypoxia. Ferroptosis is a crucial event in myocardial injury, and icariin (ICA) exerts protective effects against myocardial injury.Here, we investigated the protective mechanism of ICA in hypoxia/reoxygenation (H/R)-induced ferroptosis of cardiomyocytes. H9C2 cells were subjected to H/R induction. The content of lactate dehydrogenase (LDH) and the levels of oxidative stress and intracellular ferrous ion Fe 2+ were measured. The levels of ferroptosis markers (ACSL4 and GPX4) were detected. H/R-induced H9C2 cells were cultured with ICA in the presence or absence of ferroptosis inducer (erastin).Znpp (an HO-1 inhibitor) was added to ICA-treated H/R cells to verify the role of the Nrf2/HO-1 pathway. H/R-induced H9C2 cells showed reduced viability, enhanced oxidative stress and LDH content, increased levels of Fe 2+ and ACSL4, and decreased levels of GPX4. ICA inhibited H/R-induced ferroptosis and oxidative stress in cardiomyocytes. Erastin treatment reversed the inhibitory effect of ICA on ferroptosis in H/R cells. The expression of Nrf2 and HO-1 in H/R-induced H9C2 cells was reduced, while ICA treatment reversed this trend. Inhibition of the Nrf2/HO-1 pathway reversed the protective effect of ICA on H/R-induced ferroptosis.Collectively, our results suggest that ICA attenuates H/R-induced ferroptosis of cardiomyocytes by activating the Nrf2/HO-1 signaling pathway.
Chronic stress is a known risk factor for both endothelial dysfunction and cardiovascular disease (CVD), but less is known of how acute mental stress affects the vasculature. In this systematic review and meta-analysis, we analyzed the impact of acute mental stress on flow-mediated dilation (FMD), an indicator of endothelial function. We searched the Medline, Cochrane, EMBASE, and ISI Web of Knowledge databases through May 2014, to identify publications in English-language journals. The primary outcome was the change in FMD from baseline to the time of measurement. We also assessed the risk of bias and the heterogeneity of included studies. Our search identified eight prospective studies, which displayed significant heterogeneity. Four studies measured FMD while the subject was performing the task; six measured FMD after the task had been completed. The total number of participants was 164. The pooled results indicate that FMD did not change significantly while the task was being performed (pooled difference in means: -0.853; 95 % confidence interval (CI), -3.926/2.220; P = 0.586); however, FMD measured after the task was completed was significantly less than baseline (pooled difference in means: -2.450; 95 %CI, -3.925/-0.975; P = 0.001). In conclusions, our findings provide evidence that an acute stressful experience has a delayed, negative impact on the function of the endothelium. Repeated exposure to short-term stress may lead to permanent injury of the vasculature. Therefore, assessment of patients' exposure to both repeated acute mental stress and chronic stress may be useful in determining their risk of developing CVD.
Objective Coronavirus disease 2019 (COVID-19) is a major challenge facing the world. Certain guidelines issued by National Health Commission of the People's Repubilic of China recommend intravenous immunoglobulin (IVIG) for adjuvant treatment of COVID-19. However, there is a lack of clinical evidence to support the use of IVIG. Methods This single-center retrospective cohort study included all adult patients with laboratory-confirmed severe COVID-19 in the Respiratory and Critical Care Unit of Dabie Mountain Regional Medical Center, China. Patient information, including demographic data, laboratory indicators, the use of glucocorticoids and IVIG, hospital mortality, the application of mechanical ventilation, and the length of hospital stay was collected. The primary outcome was the composite end point, including death and the use of mechanical ventilation. The secondary outcome was the length of hospital stay. Results Of the 285 patients with confirmed COVID-19, 113 severely ill patients were included in this study. Compared to the non-IVIG group, more patients in the IVIG group reached the composite end point [12 (25.5%) vs 5 (7.6%), P = 0.008] and had longer hospital stay periods [23.0 (19.0–31.0) vs 16.0 (13.8–22.0), P < 0.001]. After adjusting for confounding factors, differences in primary outcomes between the two groups were not statistically significant (P = 0.167), however, patients in the IVIG group had longer hospital stay periods (P = 0.041). Conclusion Adjuvant therapy with IVIG did not improve in-hospital mortality rates or the need for mechanical ventilation in severe COVID-19 patients. Our study does not support the use of immunoglobulin in patients with severe COVID-19 patients.
Calycosin (CAL) is the main active component present in Astragalus and reportedly possesses diverse pharmacological properties. However, the cardioprotective effect and underlying mechanism of CAL against doxorubicin- (DOX-) induced cardiotoxicity need to be comprehensively examined. Herein, we aimed to investigate whether the cardioprotective effects of CAL are related to its antipyroptotic effect. A cardiatoxicity model was established by stimulating H9c2 cells and C57BL/6J mice using DOX. In vitro, CAL increased H9c2 cell viability and decreased DOX-induced pyroptosis via NLRP3, caspase-1, and gasdermin D signaling pathways in a dose-dependent manner. In vivo, CAL-DOX cotreatment effectively suppressed DOX-induced cytotoxicity as well as inflammatory and cardiomyocyte pyroptosis via the same molecular mechanism. Next, we used nigericin (Nig) and NLRP3 forced overexpression to determine whether CAL imparts antipyroptotic effects by inhibiting the NLRP3 inflammasome in vitro. Furthermore, CAL suppressed DOX-induced mitochondrial oxidative stress injury in H9c2 cells by decreasing the generation of reactive oxygen species and increasing mitochondrial membrane potential and adenosine triphosphate. Likewise, CAL attenuated the DOX-induced increase in malondialdehyde content and decreased superoxide dismutase and glutathione peroxidase activities in H9c2 cells. In vivo, CAL afforded a protective effect against DOX-induced cardiac injury by improving myocardial function, inhibiting brain natriuretic peptide, and improving the changes of the histological morphology of DOX-treated mice. Collectively, our findings confirmed that CAL alleviates DOX-induced cardiotoxicity and pyroptosis by inhibiting NLRP3 inflammasome activation in vivo and in vitro.
Background and Objective: Heart failure (HF) is a global public health problem with high morbidity, readmission, and mortality rates. The central mediators of cardiomyocyte survival and death are mitochondria. Mitochondria are a key therapeutic target for HF and are closely involved in the pathophysiological process of HF. A recent study proposes that cuproptosis, a novel cell death mechanism, is closely related to mitochondrial respiration. Therefore, this study aims to explore the link between cuproptosis and HF, and to find novel therapeutic targets and treatments for HF.Methods: A literature search (up to April 2022) was conducted through PubMed database, and the search range was limited to publications in English. After further literature search and screening, we found that we are currently the first study to explore the association between HF and cuproptosis.
Objective Coronavirus disease 2019 (COVID-19) is a major challenge facing the world. Certain guidelines recommend intravenous immunoglobulin (IVIG) for adjuvant treatment of COVID-19. However, there is a lack of clinical evidence to support the use of IVIG.Methods This single-center retrospective cohort study included all adult patients with laboratory-confirmed severe COVID-19 in the Respiratory and Critical Care Unit of Dabie Mountain Regional Medical Center, China. Patient information, including demographic data, laboratory indicators, the use of glucocorticoids and IVIG, hospital mortality, the application of mechanical ventilation, and the length of hospital stay was collected. The primary outcome was the composite end point, including death and the use of mechanical ventilation. The secondary outcome was the length of hospital stay.Results Of the 285 patients with confirmed COVID-19, 113 severely ill patients were included in this study. Compared with the non-IVIG group, more patients in the IVIG group reached the composite end point [12 (25.5%) vs 5 (7.6%), P=0.008]. However, there was no statistically significant difference in the primary outcome between the two groups (P=0.167) after adjusting for confounding factors. Patients in the IVIG group had a longer hospital stay [23.0 (19.0-31.0) vs 16.0 (13.8-22.0), P<0.001]. After adjusting for confounding factors, there was still a statistically significant difference between the two groups (P=0.041).Conclusion Adjuvant therapy with IVIG did not improve the in-hospital mortality rate or the need for mechanical ventilation in patients with severe COVID-19. In contrast, the application of IVIG was related to a longer hospital stay.
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