Immune responses are somewhat suppressed in immune privileged sites, including the testes, which provide a preexisting opportunity to prolong allograft survival. Previous studies have shown that intratesticular islet allografts enjoy extended survival even without any immunosuppression. However, it is unknown if testicular immune privilege can be exploited to prolong the survival of a solid allograft, including the skin, because it is impractical to implant a solid tissue in human testes.To immunize recipient mice, splenocytes from BALB/c mice were injected into the testis of C57BL/6 recipients 1 week before skin transplantation. CD8 + CD122+ and CD4 + FoxP3+ regulatory T [Treg] cells were quantified by fluorescence-activated cell sorting.Although donor-antigen inoculation alone did not delay skin allograft rejection, it significantly extended the allograft survival when combined with CD40/CD40L or B7/CD28 costimulatory blockade and further induced long-term skin allograft acceptance when both costimulatory pathways were blocked. Similarly, donor-antigen inoculation suppressed alloreactive T cell proliferation in draining lymph nodes of skin recipients in the presence of the same costimulatory blockade. Interestingly, donor-antigen inoculation via intratesticular injection increased CD8 + CD122+, but not CD4 + FoxP3+, Treg numbers after transplantation. However, both CD8 + CD122+ and CD4 + CD25+ Treg cells induced by donor-antigen inoculation and the costimulatory blockade were more potent in suppression than that induced without the inoculation. Depletion of CD8+ or CD25+ T cells largely abrogated long-term skin allograft survival induced by donor-antigen inoculation and the costimulatory blockade.Intratesticular inoculation with donor antigens promotes long-term skin allograft survival induced by conventional costimulatory blockade via the induction of both CD8 + CD122+ and CD4 + CD25+ Treg cells.
Objective: To evaluate relevant risk factors for adverse fetal outcomes among patients with Intrahepatic Cholestasis of Pregnancy (ICP).
Methods: We performed a retrospective analysis, data were obtained for all women with ICP admitted to hospital between January 2014 to December 2015. Patients were divided into group A (no adverse fetal outcomes) and group B (adverse fetal outcomes). They were further divided into mild ICP and severe ICP on the basis of severity. The frequency of adverse fetal outcomes was assessed.
Results: Among 313 eligible women, 223 (71.2%) were mild ICP and 90 (28.8%) were severe ICP. By multivariate regression logistic analysis, Total Bile Acid (TBA) and twin pregnancy were the risk factors for adverse fetal outcomes among patients (p=0.001 and p<0.001, respectively). Receiver operating characteristic curve analysis revealed that the level TBA could be used as a predictor of adverse fetal outcomes with a 59.7% sensitivity and a 56.3% specificity when the cut-off value was 24.1 μmol/L at the time of diagnosis of ICP.
Conclusion: Patients with severe ICP, twin pregnancy and high TBA level should be considered more intensive surveillance for possible adverse fetal outcomes.
Abstract It has been hypothesized that human cytomegalovirus (HCMV) infection, especially in monocyte and CD34 (+) myeloid cells, acts as a important regulator of immune system to promote inflammation in multiple autoimmune diseases. The aim of this study was to elucidate the HCMV gene expression profiles in the peripheral blood mononuclear cells (PBMCs) of SLE patients and demonstrate the effect and mechanism of viral gene associated with SLE in mono-macrophages functions. Using two RNA-Seq techniques in combination with RT-PCR, 11 viral genes mainly associated with latent HCMV infection were identified in the PBMCs of SLE patients. Among these viral genes, US31 with previously unknown function was highly expressed in the PBMCs of SLE patients compared to healthy controls. Analysis of function indicated that US31 expression could induce inflammation in monocyte and macrophage and stimulate macrophage differentiation toward an M1 macrophage phenotype. Screening via protein chips in combination with bioinformatic analysis and consequent detection of mono-macrophages function indicates that the direct interaction between US31 and NF-κB2 contributed the NF-kB2 activation. Consequent analysis indicated US31 directly interacted with NF-κB2, contribute to the polyubiquitination of the phosphorylated p100 and consequent activation of NF-κB2. Taken together, our data uncovered a previously unknown role of the HCMV protein US31 in inducing NF-κB-mediated mono-macrophage inflammation in the pathogenesis and development of SLE. Our findings provide a foundation for the continued investigation of novel therapeutic targets for SLE patients.
Abundant clinical, epidemiological, imaging, genetic, molecular and pathophysiological data together indicate that there occur an unusual inflammatory reaction and a disruption of the innate-immune signaling system in Alzheimer's disease (AD) brain. Despite many years of intense study the origin and molecular mechanics of these AD-relevant pathogenic signals are still not well understood. Here we provide evidence that an intensely pro-inflammatory bacterial lipopolysaccharide (LPS), part of a complex mixture of pro-inflammatory neurotoxins arising from abundant Gram-negative bacilli of the human gastrointestinal (GI) tract, are abundant in AD affected brain neocortex and hippocampus. For the first time we provide evidence that LPS immuno-histochemical signals appear to aggregate in clumps in the parenchyma in control brains, and in AD about 75% of anti-LPS signals were clustered around the periphery of DAPI-stained nuclei. As LPS is an abundant secretory-product of Gram-negative bacilli resident in the human GI-tract, these observations suggest (i) that a major source of pro-inflammatory signals in AD brain may originate from internally-derived noxious exudates of the GI-tract microbiome; (ii) that due to aging, vascular deficits or degenerative disease these neurotoxic molecules may 'leak' into the systemic circulation, cerebral vasculature and on into the brain; and (iii) that this internal source of microbiome-derived neurotoxins may play a particularly strong role in shaping the human immune system and contributing to neural degeneration, particularly in the aging CNS. This 'Perspectives' paper will further highlight some very recent developments that implicate GI-tract microbiome-derived LPS as an important contributor to inflammatory-neurodegeneration in the AD brain
In recent years, the mechanism of cell death has become a hotspot in research on the pathogenesis and treatment of cardiovascular disease (CVD). Different cell death modes, including autophagy, apoptosis, and pyroptosis, are mosaic with each other and collaboratively regulate the process of CVD. This review summarizes the interaction and crosstalk of key pathways or proteins which play a critical role in the entire process of CVD and explores the specific mechanisms. Furthermore, this paper assesses the interrelationships among these three cell deaths and reviews how they regulate the pathogenesis of CVD. By understanding how these three cell death modes go together we can learn about the pathogenesis of CVD, which will enable us to identify new targets for preventing, controlling, and treating CVD. It will not only reduce mortality but also improve the quality of life.
Objective To determine the effect of interferon-gamma (IFN-γ) on the phagocytosis and killing activity of a murine macrophage cell line RAW264.7 against T.asahii,and to estimate the possibility of treating T.asahii infection with IFN-γγ.Methods T.asahii was cultured with or without the presence of different concentrations (10,100,1000 U/ml) of IFN-γfor 18 hours followed by the incubation with RAW264.7 cells for different durations.After additional culture for 45 minutes,the number of T.asahii cells phagocytosed by RAW264.7 cells was counted under an inverted microscope,and the rate of phagocytosis was calculated.The number of colony forming units of T.asahii per milliliter (cfu/ml) was counted after 4-hour additional culture and the growth inhibition rate was determined.Data were processed by the SPSS 16.0 software,and comparisons of parameters between these groups were done by Bonferroni method and analysis of variance after homogeneity test of variance.Results The number of phagocytosed T.asahiicells was 25.12 ± 1.81,35.88 ± 3.56,52.12 ± 3.23,with the phagocytosis rate being 25.12％,35.88％ and 52.12％,respectively in RAW264.7 cells incubated with IFN-γ of 10,100,1000 U/ml,significantly different from that in untreated RAW264.7 cells (13.62 ± 2.39,13.62％,all P ＜ 0.01).The colony forming units of T.asahii per ml after incubation with untreated RAW264.7 cells differed significantly from those after incubation with IFN-γ (10,100,1000 U/ml)-treated RAW264.7 cells ((68.12 ± 3.39) × 500 vs.(58.62 ± 4.89) × 500,(45.50 ± 3.02) × 500 and (34.62 ± 4.24) × 500,all P＜0.01),with the growth inhibition rate being 25.21％,41.95％ and 55.83％ respectively for RAW264.7 cells incubated with IFN-γ of 10,100,1000 U/ml.Statistical differences were also observed in the killing activity between RAW264.7 cells incubated with different concentrations of IFN-γ (all P ＜ 0.01).Conclusion IFN-γ (10-1000 U/ml) may enhance the phagocytosis and killing activity of RAW264.7 cells against T.asahii in a concentration-dependent manner.
Key words:
Interferon type Ⅱ ; Macrophages; Trichosporon
A new dynamic optimal economy gain method which includes time-interval algorithm and switches' action times-exceeding restriction dynamic algorithm is proposed, and which makes a target of reaching a maximum economy income in some period of time. It decreases the number of reconfigurations by the means of combining some time-interval static reconfigurations and thus makes actual operation and control for reconfigurations possible. The results of 33-bus and 69-bus test systems prove its significance. (6 pages)
The new biochemical indicator ischaemia modified albumin (IMA) cmay reflect the degree of myocardial ischaemia sensitively. We studied the variation of ischaemia as assessed by the change in level of IMA during the transient myocardial ischaemia due to balloon dilation during PCI.
Methods
Thirty one patients who were ready to undergo PCI were randomly selected. The IMA was detected with ACB (albumin cobalt binding) test before and after saccule dilation. To study if the IMA level after saccule dilation was high than before, and if the change had statistical significance, we used Paired-Sample T test in the SPSS statistics software.
Results
The data was signed by means of (mean±SD), the IMA level before saccule dilation was (77.03±13.82) U/ml and after was (90.06±23.58) U/ml. To analyse the data, we found the IMA level after dilation was higher than that before, and the difference had statistical significance (p=0.011, obviously <0.05).
Conclusion
Balloon dilation was an ideal model of transient myocardial ischaemia which can be reflected by the change of the IMA level. We were able to cofirm the value of IMA as a new biochemical indicator on the detection of myocardial ischaemia during balloon dilation.
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