ABSTRACT
BACKGROUND: Allograft rejection remains a major obstacle to long-term graft survival. Although previous studies have demonstrated that IL-37 exhibited significant immunomodulatory effects in various diseases, research on its role in solid organ transplantation has not been fully elucidated. In this study, the therapeutic effect of recombinant human IL-37 (rhIL-37) was evaluated in a mouse cardiac allotransplantation model. METHODS: The C57BL/6 recipients mouse receiving BALB/c donor hearts were treated with rhIL-37. Graft pathological and immunohistology changes, immune cell populations, and cytokine profiles were analyzed on postoperative day (POD) 7. The proliferative capacities of Th1, Th17, and Treg subpopulations were assessed in vitro. Furthermore, the role of the p-mTOR pathway in rhIL-37-induced CD4+ cell inhibition was also elucidated. RESULTS: Compared to untreated groups, treatment of rhIL-37 achieved long-term cardiac allograft survival and effectively alleviated allograft rejection indicated by markedly reduced infiltration of CD4+ and CD11c+ cells and ameliorated graft pathological changes. rhIL-37 displayed significantly less splenic populations of Th1 and Th17 cells, as well as matured dendritic cells. The percentages of Tregs in splenocytes were significantly increased in the therapy group. Furthermore, rhIL-37 markedly decreased the levels of TNF-α and IFN-γ, but increased the level of IL-10 in the recipients. In addition, rhIL-37 inhibited the expression of p-mTOR in CD4+ cells of splenocytes. In vitro, similar to the in vivo experiments, rhIL-37 caused a decrease in the proportion of Th1 and Th17, as well as an increase in the proportion of Treg and a reduction in p-mTOR expression in CD4+ cells. CONCLUSIONS: We demonstrated that rhIL-37 effectively suppress acute rejection and induce long-term allograft acceptance. The results highlight that IL-37 could be novel and promising candidate for prevention of allograft rejection.
Subject(s)
Allografts , Graft Rejection , Heart Transplantation , Interleukin-1 , Mice, Inbred BALB C , Mice, Inbred C57BL , Recombinant Proteins , Animals , Graft Rejection/immunology , Graft Rejection/prevention & control , Humans , Mice , Recombinant Proteins/pharmacology , Interleukin-1/metabolism , Graft Survival/drug effects , Graft Survival/immunology , Th1 Cells/immunology , Th1 Cells/drug effects , Th17 Cells/immunology , Th17 Cells/drug effects , T-Lymphocytes, Regulatory/immunology , T-Lymphocytes, Regulatory/drug effects , Male , TOR Serine-Threonine Kinases/metabolism , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/drug effects , Signal Transduction/drug effectsABSTRACT
This work describes how dark fermentation (DF), anaerobic digestion (AD) and microbial fuel cells (MFC) and solid-liquid separation can be integrated to co-produce valuable biochemicals (hydrogen and methane), bioelectricity and biofertilizers. Two integrated systems (System 1: AD+MFC, and System 2: DF+AD+MFC) are described and compared to a traditional one-stage AD system in converting a mixture (COD=124±8.1gO2kg(-1)Fresh Matter) of swine manure and rice bran. System 1 gave a biomethane yield of 182 LCH4kg(-1)COD-added, while System 2 gave L yields of bio-hydrogen and bio-methane of 27.3±7.2LH2kg(-1)COD-added and 154±14LCH4kg(-1)COD-added, respectively. A solid-liquid separation (SLS) step was applied to the digested slurry, giving solid and liquid fractions. The liquid fraction was treated via the MFC-steps, showing power densities of 12-13Wm(-3) (500Ω) and average bioelectricity yields of 39.8Whkg(-1)COD to 54.2Whkg(-1)COD.
Subject(s)
Biofuels/analysis , Hydrogen/analysis , Manure/analysis , Methane/analysis , Oryza/chemistry , Animals , Bioelectric Energy Sources , Bioreactors , Fermentation , Sus scrofaABSTRACT
OBJECTIVE: To investigate the clinicopathological characteristics and prognosis in breast cancer with brain metastasis (BCBM). METHODS: The clinical data of 137 BCBM from June 2002 to June 2008 was reviewed and analyzed. Their molecular subtypes were categorized based on detection of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER-2) expression. The focal area included 35 cases of triple-negative breast cancer (TNBC), 38 cases of HR (ER and PR) (-)/HER-2(+), 40 cases of HR(+)/HER-2(-), 24 cases of HR(+)/HER-2(+). The clinical characteristics and the outcome in patients with influence were analyzed. RESULTS: In 137 BCBM, the median overal survival after brain metastasis was 6.5 month. The median survivals of TNBC, HR(-)/HER-2(+), HR(+)/HER-2(-) and HR(+)/HER-2(+) were 5.0, 5.5, 10.0 and 9.5 months, respectively. The median survivals after brain metastasis of the breast cancer patients who received the combination therapy of whole brain radiation therapy (WBRT) and neurosurgery and/or stereotactic radiosurgery, received WBRT but not combination therapy and didn't receive WBRT were 15.0, 9.5 and 4.0 months, respectively. In univariate survival analysis, substyle, number of brain metastasis, brain metastasis as initial recurrence or not, brain-only metastases or not, the combination therapy status after brain metastasis were obviously correlated with the prognosis (χ(2) = 6.891 to 29.414, P < 0.05). Substyle (RR = 1.234, 95%CI: 1.057 to 1.440) and the combination therapy status after brain metastasis (RR = 1.838, 95%CI: 1.389 to 2.431) were independent prognostic factor in multivariable analysis (P < 0.05). CONCLUSIONS: TNBC confers a high risk of death after brain metastases. Systemic treatment via combined modalities are helpful for breast cancer patients, even after the detection of brain metastases.
