Antifungal activity of nisin against clinical isolates of azole-resistant Candida tropicalis.

The rapid emergence of invasive infections caused by azole-resistant Candida tropicalis has become a public health concern, and there is an urgent need for alternative treatment strategies. Studies have demonstrated the antibacterial effects of nisin, a well-known peptide naturally produced by Lactococcus lactis subsp. lactis. However, there is scant information about the antifungal effect of nisin against C. tropicalis. The present study aims to investigate the in vitro antifungal activity of nisin against clinical isolates of azole-resistant C. tropicalis strains, as well as its inhibitory effect on biofilm formation. A total of 35 C. tropicalis strains isolated from patients with invasive fungal infections were divided into the azole-resistant group and the azole-sensitive group, containing 21 and 14 strains, respectively. The relative expression levels of the ERG11 and UPC2 genes in the azole-resistant group were higher than those in the azole-sensitive group (p < 0.0001), while no significant differences were observed in the expression levels of the MDR1 and CDR1 genes. The minimum inhibitory concentration of nisin against C. tropicalis ranged from 2 to 8 µg/mL. Nisin treatment inhibited the growth of azole-resistant C. tropicalis, with over a four-fold reduction in OD600 nm values observed at the 8-h time point, while it promoted the transition of C. tropicalis from the spore phase to the hyphal phase, as observed on cryo-scanning electron microscopy. The results of biofilm quantification using crystal violet staining indicated a significant decrease in OD570 nm values in the nisin-treated group compared to the controls (p < 0.0001). Among the 21 azole-resistant C. tropicalis strains, the biofilm formation was inhibited in 17 strains (17/21, 81%), and more than 85% inhibition of biofilm formation was observed in the representative strains. With regard to the molecular mechanisms, the expression of the BCR1 and UPC2 genes in the azole-resistant strains was down-regulated on nisin treatment (p < 0.05). In conclusion, we demonstrated, for the first time, that nisin has antifungal activity and significant anti-biofilm activity against clinical isolates of azole-resistant C. tropicalis strains. Based on the findings, nisin could be a promising alternative antifungal agent for combating azole-resistant C. tropicalis infections.

Decision-Making Error in Platelet Transfusion Caused by EDTA-Dependent Pseudothrombocytopenia: a Case Report and Literature Review.

BACKGROUND: Ethylenediaminetetraacetic acid-dependent pseudothrombocytopenia (EDTA-PTCP) is a rare phenomenon characterized by pseudo low platelet counts when using EDTA as anticoagulant and can result in false decision making of platelet transfusion. METHODS: An application for platelet transfusion from a patient who planned to undergo spinal surgery was received by the Department of Transfusion service. The preoperative laboratory test results showed thrombocytopenia (platelet counts: 27 x 109/L). The surgeon planned to transfuse platelets before the operation to avoid bleeding in operation due to thrombocytopenia. However, the lab technologist found that there was aggregation of platelets under the microscope. Samples used with sodium citrate and heparin as anticoagulants were rechecked. RESULTS: The platelet count of the patient was normal in sodium citrate and heparin anticoagulant tubes. The patient had no history and clinical symptoms of thrombocytopenia. Therefore, the doctor canceled the platelet order. We also reviewed the relevant literature of EDTA-PTCP. CONCLUSIONS: EDTA-PTCP is rare and may result of a wrong decision of platelet transfusion. Correct understanding and treatment of this situation can avoid unnecessary platelet transfusion.

Impact of fresh frozen plasma transfusion on mortality in extracorporeal membrane oxygenation.

BACKGROUND: Patients who receive extracorporeal membrane oxygenation (ECMO) support require substantial transfusions. Red blood cell (RBC) and platelet (PLT) transfusions have been reported to be associated with adverse outcomes in ECMO patients. However, little is known about whether the transfusion of fresh frozen plasma (FFP) is associated with mortality and morbidity among patients receiving ECMO. The aim of this study was to examine the relationship between FFP transfusion and mortality in ECMO patients and assess risk factors for the transfusion of FFP. METHODS: The clinical parameters of 116 ECMO patients were collected. The machine learning approach of the Boruta algorithm was employed to select the variables associated with ECMO patients' in-hospital mortality. Univariate and multivariate logistic regression analyses were applied to identify the association between the selected variables and in-hospital mortality. Spearman correlation and backwards stepwise multiple linear regression analyses were used to examine parameters contributing to FFP transfusion. RESULTS: Among the 116 patients who received ECMO support, the in-hospital mortality was 32.8%. The median FFP (mL/kg/d) transfusion was higher in dead patients (5.07, IQR 1.78-8.90) when compared to alive patients (2.16, IQR 0.79-4.66) (p = 0.007). After adjustment for confounders, FFP transfusion (mL/kg/d) was associated with in-hospital mortality (OR 1.09, 95% CI, 1.01-1.18; p = 0.035). Further analysis found that higher activated partial thromboplastin time (APTT), higher levels of uric acid (UA) and lower PLT counts were significant risk factors for FFP transfusion, with estimated values of 0.06 (95% CI, 0.02-0.11; p = 0.009), 0.01 (95% CI, 0.00-0.02; p = 0.003) and -0.03 (95% CI, -0.05--0.01; p = 0.007), respectively. CONCLUSION: FFP transfusion is markedly associated with in-hospital mortality among patients receiving ECMO, and higher APTT, higher levels of UA and lower PLT counts are risk factors for FFP transfusion. This suggests that better management of patients' coagulation system and kidney function may reduce the utilization of FFP, thus improving ECMO patient outcomes.

The P2X7 receptor mediates NLRP3-dependent IL-1ß secretion and promotes phagocytosis in the macrophage response to Treponema pallidum.

It is unclear whether P2X7 receptor (P2X7R) mediates NOD-like receptor family protein 3 (NLRP3)-dependent IL-1ß secretion and spirochete phagocytosis in syphilis. This study was conducted to investigate the role of P2X7R in modifying NLRP3-dependent IL-1ß secretion and regulating phagocytosis by Treponema pallidum (T. pallidum)-induced macrophages. Macrophages derived from a human acute monocytic leukemia cell line were cultured with T. pallidum. The activation of P2X7R in T. pallidum-treated macrophages occurred in a dose- and time-dependent manner. The P2X7R silencing group showed significantly decreased NLRP3 mRNA and protein levels (vs. the Tp group, P < 0.001). Similar results were observed for IL-1ß secretion using ELISA (vs. the Tp group, P < 0.001). Furthermore, P2X7R siRNA transfection significantly decreased the percentage of spirochete-positive macrophages (29.73% vs. 70.83%, P < 0.001) and spirochete internalization (mean fluorescence intensity (MFI), 9.20 vs. 19.39, P < 0.001). This finding revealed that P2X7R played a role in the induction of NLRP3-dependent IL-1ß secretion by T. pallidum-induced macrophages. Furthermore, we found that P2X7R plays an important role in IL-1ß secretion and in the promotion of T. pallidum phagocytosis by macrophages. These results may not only contribute to our understanding of the immune mechanism that is active during T. pallidum infection but may also lay the groundwork for strategies to combat syphilis.

[Chemical constituents and cytotoxicity assay research in small polar substances from Vitis thunbergii var. taiwaniana].

This article studied the chemical constituents from the aerial part of Vitis thunbergii var. taiwaniana. The 60% ethanol extract was eluted with 95% ethanol though HP-20 macroporous adsorption resin column. 12 compounds, including (1) betulinic acid, (2)2, 2, 2'-bis (4-hydroxyphenyl) propane bis (2, 3-epoxypropyl) ether, (3) eriodictyol, (4) trans-ε-viniferin, (5) (+)-cis-ε-viniferin, (6) kobophenol A, (7) ampelopsin A, (8) nepalensinol B, (9) cis-miyabenol C, (10) cis-vitisin B, (11) cis-gnetin H and (12) (+)-hopeaphenol, were separated by using normal phase silica gel, ODS, Sephdadex LH-20 column chromatographies and semi-preparative or preparative HPLC. Compounds 2, 5, 6, 8, 9, 10, 11 were separated from the genus Vitis for the first time and compounds 3, 7, 12 were separated from Vitis thunbergii var. taiwaniana for the first time. At a concentration of 50 µmol · L(-1), compound 6, 7 and 11 showed strong cytotoxicity against MCF-7 cell lines with the inhibition rate of 66.58%, 57.16%, 52.84%, respectively.