Longitudinal dynamics of gut microbiota in the pathogenesis of acute graft-versus-host disease.

AIM: The gut microbiota has been reported to be associated with acute graft-versus-host disease (aGvHD) in hematopoietic stem cell transplantation (HSCT). Dynamic surveillance of the microbiota is required to understand the detailed pathogenesis involved in the process of aGvHD. METHODS: Fecal samples were collected prospectively at four timepoints, including pre-HSCT (T1), graft infusion (T2), neutrophil engraftment (T3), and 30 days after transplantation (T4). Fecal samples were profiled by 16S ribosomal RNA gene sequencing to assess the microbiota composition. RESULTS: From the T1 to T4 timepoint, the diversity of the gut microbiota decreased, and the dominant species also changed, with a decrease in the obligate anaerobic bacteria and a shift toward a "pathogenic community". Compared with non-aGvHD patients, aGvHD patients had a lower abundance of Roseburia at T1 and a higher abundance of Acinetobacter johnsonii at T2. Furthermore, Acinetobacter johnsonii was negatively correlated with the secretion of IL-4 and TNF-α. At T3, Rothia mucilaginos was demonstrated to be linked with a decreased risk of aGvHD, which was accompanied by decreased secretion of IL-8. At T4, higher abundances of Lactobacillus paracasei and Acinetobacter johnsonii were identified to be related with aGvHD. Lactobacillus paracasei was associated with the downregulation of IL-10, and Acinetobacter johnsonii was associated with the downregulation of IL-2 and TNF-α. CONCLUSIONS: Dynamic changes in gut microbiota composition and related cytokines were found to be related to aGvHD, including pathogenic or protective changes. These findings suggested that manipulation of gut microbiota at different timepoints might be a promising avenue for preventing or treating this common complication.

Protective effects of Erdosteine on interleukin-1ß-stimulated inflammation via inhibiting the activation of MAPK, NF-κB, and Wnt/ß-catenin signaling pathways in rat osteoarthritis.

Osteoarthritis (OA), a degenerative arthropathy, is featured with progressive degradation of cartilage and a chondrocyte inflammatory response. Erdosteine (ER) showed the anti-oxidant properties and various anti-inflammatory effects in various diseases. However, whether it protects against OA remains unknown. In this study, we explore the potential therapeutic properties of ER on IL-1ß-stimulated rat chondrocytes and its underlying mechanism in vitro and vivo. Cell viability, pro-inflammatory cytokines and the degradation of ECM biomarkers were tested to determine the effects of ER at 10, 20, and 40 µM doses on IL-1ß-induced rat chondrocytes for 24 h in virto. In vivo, intra-articular injections of 50 µl of 100 mg/ml ER twice a week for 8 weeks. The results showed ER significantly suppressed the expressions of IL-1ß-induced the production of inflammatory factors in a dose-dependent pattern (4.30-fold decrease in COX-2, p < 0.05; 4.77-fold decrease in iNOS, p < 0.05 at 40 µM in protein levels). Moreover, ER could attenuate the degradation of ECM in IL-1ß-induced rat chondrocytes by repressing the expression of OA-related factors (2.40-fold decrease in ADAMTS-5, p < 0.05; 3.12-fold decrease in MMP1, p < 0.05; 3.97-fold decrease in MMP3, p < 0.05; and 2.62-fold decrease in MMP-13, p < 0.05 at 40 µM in protein levels). Furthermore, our study revealed that ER could inhibit the activations of IL-1ß-induced MAPK and Wnt/ß-catenin. Besides, ER could suppress the process of IL-1ß-induced P65 from the cytoplasm into the nucleus. In vivo, ER delaied the osteoarthritis progression in rat OA models. Collectively, ER might become a new therapeutic agent for OA.

Risk factors and antimicrobial resistance profiles of Pseudomonas putida infection in Central China, 2010-2017.

The aim of this study was to analyze the risk factors, clinical features, and antimicrobial resistance of Pseudomonas putida (P putida) isolated from Tongji Hospital in Wuhan, China.The data of 44 patients with P putida infections were retrospectively reviewed in this study. All cases of P putida strains were detected by the clinical laboratory of Tongji Hospital in the period of January 2010 to December 2017. Antimicrobial susceptibility testing was conducted using Kirby-Bauer method.Forty-four effective strains of P putida were isolated, including 32 inpatients and 12 outpatients. The 32 inpatients cases were obtained from various departments, which were urosurgery wards (n = 5, 15.6%), pediatrics wards (n = 4, 12.5%), hepatic surgery wards (n = 4, 12.5%), among others. The isolates had been discovered from urine specimens (28.2%), blood specimens (21.9%), sputum specimens (12.5%), and so on. Twenty-five patients had histories of catheterization before the isolation of P putida. Twenty-four patients were in immunocompromised states, 5 patients had undergone surgery, catheterization and were taking immunosuppressive therapy simultaneously. Polymicrobial infections were found in some P putida cases, especially Stenotrophomonas maltophilia, Pseudomonas aeruginosa, and Escherichia coli. All the patients had treated by antimicrobial before culture. Multi-drug-resistant strains were detected in 75% of P putida isolates. The P putida strains were resistant to trimethoprim/sulfamethoxazole (97.7%), aztreonam (88.6%), minocyline (74.3%), ticarcillin/clavulanic acid (72.7%), and sensitive to amikacin (86.4%), imipenem (62.8%), gentamicin (56.8%).Catheterization or other invasive procedures, immunocompromised states, and underlying diseases increased the risks of P putida infections. Moreover, the P putida strains were highly resistant to trimethoprim/sulfamethoxazole, aztreonam, minocyline, ticarcillin/clavulanic acid.