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Kusk Tate posted an update 6 months, 2 weeks ago
HDAC6/p97/HSF1.Objective To investigate the effect of N-acetylcysteine (NAC) on the proliferation of fibroblast-like synoviocytes (FLS) treated with low concentration of hydrogen peroxide (H2O2) in rats with adjuvant arthritis (AA) and its mechanism. Methods Twenty SD rats were divided into a normal group and a model group (10 rats in each group). The model group was established by subcutaneous injection of Freund’s complete adjuvant into the toe of rats, and the rats were sacrificed 28 days later. The contents of serum malondialdehyde (MDA) were detected by thiobarbituric acid method; the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were determined by hydroxylamine method and colorimetry respectively; and Nrf2 and Keap1 proteins in ankle synovial tissues of AA rats were detected by immunohistochemistry. AA-FLS were isolated, cultured, and identified by digestion of ankle joint slides of AA rats in vitro. The effects of NAC at different concentrations (final concentration 0, 0.3, 0.9, 3, 10, /Keap1 pathway.Objective To induce the differentiation of hematopoietic stem progenitor cells (HSPCs) into T cell by creating thymic organoids and simulating the three-dimensional structure of thymus tissue in vitro. Methods The retroviral vector expressing the DLL1 and Green fluorescent protein (GFP) was constructed, and the OP9-DLL1 cell line was established in OP9 cells with the aid of retroviral infection. The mRNA and protein level of DLL1 in OP9-DLL1 cells was detected by quantitative real-time PCR and Western blot respectively. Immunofluorescence assay was used to detect the DLL1 protein expression and distribution in OP9-DLL1 cells. HSPCs were extracted from E13.5 fetal liver and bone marrow of C57BL/6 mouse, and mixed with OP9-DLL1 cells in an appropriate ratio respectively, then compacted by centrifuging and cultured at the air-liquid interface in medium. Fluorescence microscope was used to observe the growth of thymic organoids. Flow cytometry was used to detect the expression of T cell surface markers, including CD3, CD4, CD8, CD25, CD44, CD45, CD117 and TCRβ. Immunofluorescence cytochemical staining was used to observe the distribution of hematopoietic cells in thymic organoids. Results The retroviral vector expressing DLL1 and GFP was successfully constructed. The OP9 cells were infected with the retrovirus constructed, and OP9-DLL1 cells were obtained by GFP screening. The mRNA and protein level of DLL1 in OP9-DLL1 cells significantly increased, and DLL1 was expressed in the membrane OP9-DLL1 cells. During the 40 days of culture, the thymic organoids remained in good condition and increased gradually in volume. The thymic organoids induced programmed differentiation of T cells, and differentiation of HSPCs into CD3+ T cells. Conclusion OP9-DLL1 cells can be used to construct thymic organoids and to induce differentiation of HSPCs into T cells in vitro.Objective To investigate the role of Notch signaling in regulating the polarization of macrophages with signal regulatory protein α (SIRPα). Methods RAW264.7 cells were polarized into M1 phenotype after being treated with lipopolysaccharides (LPS) and interferon γ (IFN-γ) and into M2 phenotype with interleukin-4(IL-4). The mRNA levels of tumor necrosis factor α (TNF-α), IL-12, IL-10, mannose receptor (MR), and SIRPα were detected by real-time quantitative PCR. The protein expression level of SIRPα was detected by Western blotting. After Notch signal was activated by gene transfection or blocked by gamma-secretase inhibitor (GSI), SIRPα expression in macrophages was detected by Western blotting. SIRPα promoter region (-2615-+123) was amplified by mouse genomic DNA, and the regulatory effect of Notch activation on SIRPα was detected by reporter gene assay. Results The expression of SIRPα decreased in M1 type macrophages and increased in M2 type macrophages. Notch signaling inhibited the expression of SIRPα in macrophages, while GSI increased the expression of SIRPα in macrophages. Reporter gene assay confirmed that Notch activation significantly inhibited luciferase expression driven by SIRPα promoter fragment. Conclusion Notch signaling involves the M1-type polarization of macrophages by inhibiting the expression of SIRPα.
Urine cultures have poor specificity for catheter-associated urinary tract infections (CAUTIs). We evaluated the effect of a urine-culture stewardship program on urine culture utilization and CAUTI in adult intensive care units (ICUs).
A quasi-interventional study was performed from 2015 to 2017.
The study cohort comprised 21,367 patients admitted to the ICU at a teaching hospital.
The urine culture stewardship program included monthly 1-hour discussions with ICU house staff emphasizing avoidance of “pan-culture” for sepsis workup and obtaining urine culture only if a urinary source of sepsis is suspected. The urine culture utilization rate metric (UCUR; ie, no. urine cultueres/catheter days ×100) was utilized to measure the effect. Disodium Phosphate mw Monthly UCUR, catheter utilization ratio (CUR), and CAUTI rate were reported on an interactive quality dashboard. To ensure safety, catheterized ICU patients (2015-2016) were evaluated for 30-day readmission for UTI. Time-series data and relationships were analyzed using Spearman correlation coefficients and regression analysis.
Urine culture utilization decreased from 3,081 in 2015 to 2,158 in 2016 to 1,218 in 2017. CAUTIs decreased from 78 in 2015 to 60 in 2016 and 28 in 2017. Regression analysis over time showed significant decreases in UCUR (r, 0.917; P < .0001) and CAUTI rate (r, 0.657; P < .0001). The co-correlation between UCUR and CAUTI rate was (r, 0.625; P < .0001) compared to CUR and CAUTI rate (r, 0.523; P = .004). None of these patients was readmitted with a CAUTI.
Urine culture stewardship program was effective and safe in reducing UC overutilization and was correlated with a decrease in CAUTIs. Addition of urine-culture stewardship to standard best practices could reduce CAUTI in ICUs.
Urine culture stewardship program was effective and safe in reducing UC overutilization and was correlated with a decrease in CAUTIs. Addition of urine-culture stewardship to standard best practices could reduce CAUTI in ICUs.