Gut microbiota composition of patients with ulcerative colitis (UC) is markedly altered compared with healthy individuals. There is mounting evidence that probiotic therapy alleviates disease severity in animal models and patients with inflammatory bowel disease (IBD). Bacillus subtilisis, as a probiotic, has also demonstrated a protective effect in IBD. However, the therapeutic mechanism of its action has yet to be elucidated. In the present study, a dextrose sulfate sodium (DSS)-induced UC mouse model was used to investigate the role of B. subtilis in the restoration of gut flora and determine its effective dose. Mucosal damage was assessed by performing alcian blue staining, cytokine levels were analyzed by ELISA and microbiota composition was investigated using 454 pyrosequencing to target hypervariable regions V3-V4 of the bacterial 16S ribosomal RNA gene. The results demonstrated that a higher dose B. subtilisis administration ameliorated DSS-induced dysbiosis and gut inflammation by balancing beneficial and harmful bacteria and associated anti- and pro-inflammatory agents, thereby aiding intestinal mucosa recovery from DSS-induced injuries. These findings indicate that choosing the correct dose of B. subtilis is important for effective UC therapy. The present study also helped to elucidate the mechanisms of B. subtilis action and provided preclinical data for B. subtilis use in UC therapy.
ADAMTS2 (A Disintegrin and Metalloproteinase With Thrombospondin Motifs 2) is recognized as a metalloproteinase that promotes the cleavage of amino propeptides of types I, II, III, and V procollagens. However, the role of ADAMTS2 in the heart has not yet been defined. Herein, we observed the upregulated expression of ADAMTS2 in failing human hearts and hypertrophic murine hearts. Mice lacking ADAMTS2 display exacerbated cardiac hypertrophy on pressure overload-induced hypertrophic response, whereas mice with cardiac-specific overexpression of ADAMTS2 display alleviation of this detrimental phenotype. Consistent with these results, in vitro loss or gain of function experiments in neonatal rat cardiomyocytes confirmed that ADAMTS2 negatively regulates cardiomyocyte hypertrophy in response to Ang II. Mechanistically, blockage of the PI3K (phosphoinositide 3-kinase)/AKT (protein kinase B)-dependent signaling pathway with specific inhibitors both in vivo and in vitro could rescue the aggravated hypertrophic response to the loss of ADAMTS2. Collectively, we propose that ADAMTS2 regulates the hypertrophic response through inhibiting the activation of the PI3K/AKT-dependent signaling pathway. Because ADAMTS2 is an extracellular protein, it could be effectively manipulated using pharmacological means to modulate cardiac hypertrophy.
The stented elephant trunk technique in aortic arch replacement combined with transaortic stented graft implantation into the descending aorta has been introduced as a means of eliminating the residual false lumen in the descending thoracic aorta and improving long-term outcomes of surgical intervention for Debakey I aortic dissection. This report summarizes the operative and follow-up data with this new procedure. Between August 2004 and May 2009, 28 stented elephant trunk operations were performed for Debakey I aortic dissection at Nanjing First Hospital. A 10 cm long woven Dacron graft was implanted through the aortic arch during hypothermic circulatory arrest. Patent false lumina were evaluated using computed tomography three months after the operation. Mean cardiopulmonary bypass time was 213.2±47.2 min, and selected cerebral perfusion time was 38.8±9.7 min. Hospital mortality was 14.3% (4/28). Thrombus obliteration of the residual false lumen in the descending aorta was observed in 91.7% of the aortic dissections three months postoperatively. The survival rate was 87.5% at five years and the freedom from reoperation rate was 91.7%. Total aortic arch replacement combined with transaortic stented graft implantation into the descending aorta is an effective treatment for Debakey type I aortic dissection.
BackgroundThere is controversy regarding the choice of prosthetic valves in patients with cardiac valve disease and dialysis-dependent patients. This review assesses a 12-year experience and outcomes after valve replacement in patients on chronic preoperative renal dialysis, comparing survival and valve-related outcomes following valve replacement with bioprostheses versus mechanical prostheses in this population in china.MethodsFrom January 1999 and October 2011, 73 consecutive dialysis patients underwent cardiac valve replacement. The patients were divided into two groups: (Group B) bioprosthesis valves were implanted in 38 (52.1%) patients and (Group M) mechanical valves were implanted in 35 (47.9%) patients. Outcome measures included perioperative data, hospital mortality, major postoperative complications, follow-up outcomes, valve related morbidity and late survival.ResultsThere were no significant differences in terms of patient characteristics in the 2 groups. Thirty-three were isolated aortic valve replacements (45.2%); 28 were isolated mitral valve replacements (38.4%); 10 were combined aortic and mitral replacements (13.7%); 2 were combined tricuspid and mitral replacements (2.7%). The overall hospital mortality was 5.5% (n = 4) and was not different between Group B (5.3%) and Group M (5.7%). Low ejection fraction was the only independent predictors of hospital mortality. There was no significant difference between the groups in the overall rate of complications. The overall mean follow-up was 47 ± 23 months. According to the Kaplan-Meier analysis, late mortality, perivalvular leak and freedom from reoperation were similar in patients with mechanical and bioprosthesis valves. The bioprosthesis valve group had significantly higher freedom from thromboembelism-bleeding events (100% versus 77.6 ± 11.0%, p = 0.012), and valve-related morbidity (73.2 ± 10.1% versus 58.1 ± 10.9%, p = 0.035) in 5 years. Kaplan–Meier survival estimates at 1, 3, and 5 years were 0.971, 0.832, and 0.530 in group B, and 0.967, 0.848, and 0.568 in group M.ConclusionsThere is no significant difference in the perioperative morbidity and mortality, late survival of dialysis patients after cardiac valve replacement with bioprostheses versus mechanical valves. In spite of the limited sample size analyzed, its outcome and consistency to several previous reports supports a conclusion that bioprostheses rather than mechanical ones could be a favorable choice for valve replacement needs of renal failure patients.
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