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Abdominal aortic aneurysm (AAA) is a prevalent condition which causes progressive growth and rupture of aortic wall with a high death rate. Several studies have found that treatment with statins may decrease the progress of AAA and the risk of rupture by suppressing the inflammatory mediators, decreasing oxidative stress, and inhibiting mechanisms involved in extracellular matrix (ECM) degradation. Moreover, some studies have reported that prehospital therapy with statins can decrease mortality after surgery. The novelty of this paper is that different studies including those performed in humans and animals were reviewed and the potential mechanisms by which statins can have an effect on AAA were summarized. Overall, the evidence suggested an association between treatment with statins and improvement of AAA.Proanthocyanidins have been shown to inhibit the signaling pathways related to oxidative stress and inflammation, also improved cell membrane integrity. The effect of peanut skin proanthocyanidins (PSPc) on CD remains unknown. In this paper, the effect and mechanism of PSPc on glial protein-induced Caco-2 cytotoxicity were studied. The results showed that PSPc may inhibit oxidative stress in DPG-induced CD model in vitro by regulating SIRT1/NRF2 pathway. By regulating SIRT1 and IκB signaling pathways, inhibit the phosphorylation of NF-κB and the deacetylation of NF-κB, inhibit inflammatory response, reduce release of inflammatory cytokines (IL-1β, IL-6, TNF-α), the cell survival rate was and the expression of TGM2 were improved, avoiding the damage of cell monolayer model. This experiment proved the prominent effect of PSPc on CD intervention. Studying the mechanism of PSPc in the treatment of CD injury will contribute to explore new therapies for CD which will be of great significance to supplement or replace gluten-free diets.Feruloyl esterase is a subclass of α/β hydrolase, which could release ferulic acid from biomass residues for use as an efficient additive in food or pharmaceutical industries. In the present study, a feruloyl esterase with broad substrate specificity was characterised and secreted by Bacillus subtilis WB600. After codon usage optimisation and signal peptide library screening, the secretion amount of feruloyl esterase was enhanced by up to 10.2-fold in comparison with the base strain. The site-specific amino acid substitutions that facilitate protein folding further improved the secretion by about 1.5-fold. Selleckchem PMX-53 The purified rationally designed enzyme exhibited maximal activity against methyl ferulate at pH 6.5 and 65 °C. In the solid-state fermentation, the genetically engineered B. subtilis released about 37% of the total alkali-extractable ferulic acid in maize bran. This study provides a promising candidate for ferulic acid production and demonstrates that the secretion of a heterologous enzyme from B. subtilis can be cumulatively improved by changes in protein sequence features.
To evaluate the activity of meropenem-amikacin and meropenem-colistin combinations with checkerboard broth microdilution (CKBM) compared with isothermal microcalorimetry (ITMC) assays against a multi-centric collection of multi-drug-resistant Gram-negative clinical isolates; and to compare the fractional inhibitory concentration (FIC) index and time to results of CKBM and ITMC.
A collection of 333 multi-drug-resistant Gram-negative clinical isolates showing reduced susceptibility to meropenem (121 Klebsiella pneumoniae, 14 Escherichia coli, 130 Pseudomonas aeruginosa and 68 Acinetobacter baumannii) isolated from different centres (Florence, Madrid, Rotterdam and Stockholm) was included in the study. The antimicrobial activity of meropenem-amikacin and meropenem-colistin combinations was evaluated with CKBM and ITMC. FIC index results were interpreted as synergistic/additive and indifferent for values ≤0.5/0.5<x≤1 and >1, respectively. Whole-genome sequencing data of a subset of strains were used to ant Gram-negative clinical isolates, and could be implemented for the rapid evaluation of in-vitro activity of antimicrobial combinations.
It is unknown whether infectious diseases consultation improves outcomes for enterococcal bacteraemia in a multicentre healthcare system.
This retrospective multicentre observational cohort study included 250 adult patients with enterococcal bacteraemia between July 2016 and December 2020. The primary endpoint was a composite of clinical failure, including persistent bacteraemia, persistent fever, and in-hospital mortality. Secondary endpoints included adherence to a treatment bundle (appropriate empiric and definitive antibiotics, appropriate planned treatment duration, obtaining repeat blood cultures and an echocardiogram).
Clinical failure occurred in 35 of 155 patients (22.6%) with an infectious diseases consultation and 16 of 95 patients (16.8%) without an infectious diseases consultation (P=0.274). Multivariate analysis identified vasopressors as the only independent predictor of the primary outcome. Infectious diseases consultation resulted in higher adherence to a treatment bundle, including echocardiogram (75.5% vs. 34.7%; P < 0.0001), repeat blood cultures (85.2% vs. 68.4%; P=0.002), appropriate definitive antibiotics (70.5% vs. 91.6%; P < 0.0001) and appropriate planned durations of therapy (81.1% vs. 94.2%; P=0.001). More patients in the consult group were treated with ampicillin (47.1% vs. 22.1%; P < 0.0001) and fewer were treated with vancomycin (17.4% vs. 24.2%; P=0.068).
Despite finding no difference in clinical failure between groups, this study highlights important benefits of infectious diseases consultation in enterococcal bacteraemia.
Despite finding no difference in clinical failure between groups, this study highlights important benefits of infectious diseases consultation in enterococcal bacteraemia.Daptomycin (DAP) is indicated for difficult-to-treat Gram-positive infections, especially those caused by methicillin-resistant Staphylococcus aureus (MRSA). Exposure of S. aureus to subinhibitory antimicrobial concentrations (sub-MICs) has been shown to alter cell morphology and biofilm formation. This study aimed to investigate the influence of DAP biofilm sub-MICs on the damage caused by human polymorphonuclear neutrophils (PMNs) against MRSA biofilms and the potential immunomodulatory activity of DAP on human monocytes (MNCs) exposed to MRSA biofilms. DAP activity against biofilms and the impact of DAP on PMN-induced biofilm damage were evaluated by the XTT reduction assay, whereas pathogen recognition, signal transduction and cytokine modulation of DAP on MNCs in response to MRSA biofilms were assessed by RT-PCR and ELISA methodology. The MIC50 of DAP to MRSA biofilms was 16-32 mg/L. Pre-treatment of MRSA with 1, 2 or 4 mg/L DAP caused a synergistic effect on PMN-mediated biofilm damage, being dependent on the effector-to-target ratio. MNCs responded to MRSA biofilms and DAP through Toll like receptor 2 (TLR2) upregulation and increased NLRP3 inflammasome production. DAP caused 2.5-fold greater TLR2 mRNA levels than those caused by MRSA biofilms. A predominantly inflammatory response was induced by either component, causing the release of significantly increased IFN-γ, TNF-α, IL-8 and IL-6 levels by MNCs exposed to the combination treatment. MRSA biofilms alone or combined with DAP caused low amounts of IL-10 production, but increased IL-1β levels. DAP may condition MNCs towards an inflammatory response through TLR2 engagement and NLRP3 inflammasome activation, possibly controlling biofilm-associated pathogenicity.One hundred and five uropathogenic Escherichia coli (UPEC) strains from patients with community-acquired urinary tract infections were characterized according to phylogenetic group, virulence factors, serogroup, antibiotic resistance, and genotype. The pathogenic phylogenetic groups (B2, D, and F) were found in 71.4% of the tested strains. Among them, the main uropathogenic serogroups were O8, O25, and O75, in which 97.1% of the strains had a multidrug-resistant profile. Sixteen virulence genes were analysed using a combination of polymerase chain reaction (PCR) assays, with the fimH, irp-2, iutA, aer, iucC, PAI, sat, iroN, usp, and cnf1 genes being mainly found in pathogenic phylogroups. The E. coli O25b-ST131 clone was identified in 32% of the strains assigned to the pathogenic phylogroup B2. These findings demonstrate that virulence genes encoding adhesin components, iron-acquisition systems, toxins, and pathogenicity-associated islands were highly prevalent among the pathogenic phylogroup of UPEC strains.
Eugenia uniflora Linn (Myrtaceae) is the native species of Brazil. The leaves of this species are used in folk medicine to treat different inflammatory and gastrointestinal disorders. However, research on the safety of using E. uniflora leaves has been poorly explored.
This approach aims to investigate the phytochemical composition as well as the acute, subacute toxicity, and in vivo genotoxic profile of the aqueous extract of E. uniflora leaves.
The chemical composition of E. uniflora leaf extract was determined by Fingerprint by High-Performance Thin Layer and High-Performance Liquid Chromatography. The acute toxicity in vivo was evaluated for 14 days after the administration of E. uniflora leaves extract (2000mg/kg). For the evaluation of subacute toxicity, mice were daily treated for 28 days with E. uniflora extract (250, 500, or 1000mg/kg). Signs of behavioral toxicity and biochemical and hematological alterations, including the multiple organ toxicities were investigated. In addition, the micronucth non-toxic and non-genotoxic action in vivo. This approach sheds light on the chemical composition of the leaves of E. uniflora and suggests a high margin of safety in the popular use of the leaves of this plant species.
Dahuang Mudan decoction (DMD) is a classic prescription for treating intestinal carbuncle from Zhang Zhongjing's "Essentials of the Golden Chamber" in the Han Dynasty. Recent studies also prove that DMD has a therapeutic effect on ulcerative colitis (UC), but its mechanism is still unclear.
In this study, we aim to assess the therapeutic effect of DMD on DSS-induced chronic colitis in mice and deeply expound its underlying regulative mechanism.
The efficacy of DMD on mice with 2% DSS-induced chronic colitis was examined by changes in mouse body weight, DAI score, colon length changes, peripheral blood white blood cells (WBC) and red blood cells (RBC) counts, and hemoglobin (HGB) content, using mesalazine as a positive control. A small animal imaging system observed the FITC-Dextran fluorescence distribution in mice, and the contents of IL-22 and IL-17A in colon tissue homogenate supernatant and LPS in peripheral blood were detected by ELISA. Fluorescence in situ molecular hybridization and bacterial culcell infiltration. Moreover, DMD decreased LPS content in serum, bacterial infiltration of colonic mucosa, and bacterial translocation in spleen and mesenteric lymph nodes. Simultaneously, DMD intensified the expression of ZO-1, Occludin, and Claudin-1, the ratio of NCR
ILC3 and IL-22
ILC3, and decreased the proportion of NCR
ILC3. In vitro studies also confirmed that the conditioned medium of DMD promoted the migration of Caco-2cells and the expression of tight junction proteins.
Our results confirm that DMD improves inflammation and restores intestinal epithelial function in mice with chronic colitis, and the mechanism may be related to regulating ILC3 function.
Our results confirm that DMD improves inflammation and restores intestinal epithelial function in mice with chronic colitis, and the mechanism may be related to regulating ILC3 function.
My Website: https://www.selleckchem.com/products/pmx-53.html
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