Antimutagenic Effects of Selenium-Enriched Polysaccharides from Pyracantha fortuneana through Suppression of Cytochrome P450 1A Subfamily in the Mouse Liver.

Both selenium (Se) and polysaccharides from Pyracantha fortuneana (Maxim.) Li (PFPs) (P. fortuneana) have been reported to possess antioxidative and immuno-protective activities. Whether or not Se-containing polysaccharides (Se-PFPs) have synergistic effect of Se and polysaccharides on enhancing the antioxidant and immune activities remains to be determined. We previously reported that polysaccharides isolated from Se-enriched P. fortuneana (Se-PFPs) possessed hepatoprotective effects. However, it is not clear whether or not they have anti-mutagenic effects. In the present study, we compared and evaluated anti-mutagenic effects of Se-PFPs at three concentrations (1.35, 2.7 and 5.4 g/kg body weight) with those of PFPs, Se alone or Se + PFPs in mice using micronucleus assay in bone marrow and peripheral blood as well as mitomycin C-induced chromosomal aberrations in mouse testicular cells. We also elucidated the underlying mechanism. Our results demonstrated that Se-PFPs inhibited cyclophosphamide (CP)-induced micronucleus formation in both bone marrow and peripheral blood, enhanced the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) in mouse liver, and reduced the activity and expression of cytochrome P450 1A (CYP4501A) in mouse liver in a dose-dependent manner. In addition, we found that the anti-mutagenic potential of Se-PFPs was higher than those of PFPs, Se alone or Se + PFPs at the same level. These results suggest that the anti-mutagenic potential of Se-PFPs may be mediated through the inhibition of the activity and expression of CYP4501A. This study indicates that application of Se-PFPs may provide an alternative strategy for cancer therapy by targeting CYP1A family.

Haploidentical donor transplant is associated with secondary poor graft function after allogeneic stem cell transplantation: A single-center retrospective study.

BACKGROUND: Secondary poor graft function (sPGF) is a serious complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT) related to poor outcome. We aimed to retrospectively evaluate the morbidity and hazard elements of sPGF after allo-HSCT. METHODS: Eight hundred and sixty-three patients who achieved initial engraftment of both neutrophils and platelets were retrospectively reviewed in this study. RESULTS: Fifty-two patients developed sPGF within 180 days post-transplants, with the median onset time was 62 days (range, 34-121 days) post-transplants. The overall cumulative incidence of sPGF within 180 days post-transplantation was 6.0%, with 3.4%, 3.4%, and 10.1%, respectively, in matched sibling donor (MSD), matched unrelated donor (MUD), and haploidentical donor (HID) transplant (p < 0.0001). Multivariable analysis showed that HID (HID vs. MSD: hazard ratio [HR] 2.525, p = 0.004; HID vs. MUD: [HR] 3.531, p = 0.017), acute graft versus host disease (aGVHD) within +30 days ([HR] 2.323, p = 0.003), and cytomegalovirus (CMV) reactivation ([HR] 8.915, p < 0.0001) within +30 days post-transplants were hazard elements of sPGF. The patients with sPGF had poorer survival than good graft function (51.7±8.1% vs. 62.9±1.9%, p < 0.0001). Our results also showed that only CMV reactivation was the hazard element for the development of PGF in HID transplant ([HR] 12.521 p < 0.0001). CONCLUSION: HID transplant is also an independent hazard element of sPGF except for aGVHD and CMV reactivation.

Autoimmune hemolytic anemia after allogeneic hematopoietic stem cell transplantation in adults: A southern China multicenter experience.

To investigate the incidence and risk factors as well as prognosis of autoimmune hemolytic anemia (AIHA) following allogeneic hematopoietic stem cell transplantation (allo-HSCT), a total of 1377 adult hematological malignancies at three institutions were enrolled in this study. The 3-year cumulative incidence of AIHA was 2.2 ± 0.4%. Multivariate analysis showed that haploidentical donors (HRDs) and chronic graft vs host disease (cGVHD) were the independent risk factors for AIHA. Patients with AIHA treated initially with corticosteroids combined with cyclosporine A (CsA) had a higher complete response rate than those with corticosteroids monotherapy (66.7% vs 11.1%; P = .013). The 3-year cumulative incidence of malignant diseases relapse was 4.4 ± 4.3% and 28.0 ± 1.3% (P = .013), treatment-related mortality (TRM) was 8.9 ± 6.3% and 17.4 ± 1.2% (P = .431), disease-free survival (DFS) was 56.1 ± 1.5% and 86.7 ± 7.2% (P = .011), and overall survival (OS) was 86.3 ± 7.4% and 64.1 ± 1.5% (P = .054), respectively, in the patients with AIHA and those without AIHA. Our results indicate that HRDs and cGVHD are risk factors for AIHA and corticosteroids combined with CsA are superior to corticosteroids as initial treatment for AIHA. Autoimmune hemolytic anemia does not contribute to increase TRM and could reduce the malignant diseases relapse and increase DFS.

Autoimmune hematological diseases following haploidentical donor hematopoietic stem cell Transplant compared with matched sibling and unrelated donor.

Autoimmune hematological diseases (AHDs) occur more frequently than other autoimmune complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and are often refractory to treatment. This study was to analyze the incidence and risk factors of AHDs as well as their response to treatment . Four hundred and forty-five adult malignant hematopoietic disorders underwent allo-HSCT were enrolled in this retrospective study, including 124 haploidentical donor (HRD), 140 unrelated donor (MUD) and 181 HLA-matched sibling donor (MSD) transplants. Twelve patients developed AHDs, including 6 autoimmune hemolytic anemia and 6 Evans syndrome. Evans syndrome all occurred in HRD transplants. The 3-year cumulative incidence of AHDs was 4.0 ± 1.3%, and HRD had higher incidence than MUD (8.7 ± 3.0% vs 1.8 ± 1.2%, P = 0.012) and MSD (8.7 ± 3.0% vs 3.5 ± 2.6%, P = 0.004 ). The steroids combined with Cyclosporine A were acted as the first line treatment, and the response rate was 73%. No patients experienced recurrence at a median follow up of 313 days after stopping treatment. HRD transplants (vs MUD: HR, 5.87; CI, 1.24 to 27.73; p = 0.026 and vs MSD: HR, 7.70; CI, 1.63 to 36.44; P = 0.010) and concurrent chronic graft versus host disease (HR, 3.76; CI, 1.18 to 11.92; P = 0.025) were risk factors for AHDs.

Meta-analysis of microRNA-146a rs2910164 G>C polymorphism association with autoimmune diseases susceptibility, an update based on 24 studies.

BACKGROUND: Published data showed that the susceptibility of autoimmune diseases (ADs) was associated with the polymorphism rs2910164 in microRNA-146a (miR-146a). However, the results remain controversial so far. Two meta-analyses published in 2013 and 2014 came to opposite conclusions. In order to derive a more precise estimation of the relationship, we performed this meta-analysis. METHODS: We searched the PubMed, OvidSP and CNKI databases (published prior to September 8th, 2014) and extracted data from eligible studies. The procedure of meta-analysis was performed by using the Stata 12.0 software. Random effect model or fixed effect model were chosen respectively, according to the between study heterogeneities. RESULTS: A total of 24 case-control studies, 11 more than previous meta-analysis on this topic, were involved. We took stratified analyses by different ethnicities and different types of diseases in different genetic models. In Caucasian subgroup, significant increased risks of GC genotype and GC+CC genotype with ADs susceptibility were found in heterozygote model (GC vs GG, OR = 1.38, 95% CI 1.04-1.83, p = 0.024) and dominant model (GC+CC vs GG, OR = 1.37, 95% CI 1.01-1.85, p = 0.041), respectively. Meanwhile, in other disease subgroup, significant increased risks of C allele, CC genotype and GC+CC genotype were found in allele model (C vs G, OR = 1.16, 95% CI 1.04-1.31, p = 0.010), homozygote model (CC vs GG, OR = 1.42, 95% CI 1.10-1.84, p = 0.006) and dominant model (GC+CC vs GG, OR = 1.25, 95% CI 1.04-1.51, p = 0.020), respectively. CONCLUSIONS: MiR-146a rs2910164 G>C polymorphism was associated with the susceptibility of ADs.

Impact of V-ets Erythroblastosis Virus E26 Oncogene Homolog 1 Gene Polymorphisms Upon Susceptibility to Autoimmune Diseases: A Meta-Analysis.

V-ets erythroblastosis virus E26 oncogene homolog 1 (ETS1) is recognized as a gene of risk to autoimmune diseases (ADs). Two single nucleotide polymorphisms (SNPs) in ETS1 (rs1128334 G>A and rs10893872 T>C) were considered associated with ADs risk. However, the results remain conflicting.We performed a meta-analysis to evaluate more precise estimations of any relationship. We searched PubMed, OvidSP, and Chinese National Knowledge Infrastructure databases (papers published prior to September 12, 2014) and extracted data from eligible studies. Meta-analysis was performed using the STATA 12.0 software. Random effect model or fixed effect model were chosen according to the study heterogeneities.A total of 11 studies including 7359 cases (9660 controls) for rs1128334 and 8 studies including 5419 cases (7122 controls) for rs10893872 were involved in this meta-analysis. Overall, our results showed that there were significant associations for rs1128334 with AD risk in 5 genetic models, both in pooled analysis and in systemic lupus erythematous (SLE) subgroup, and in 3 genetic models of the uveitis subgroup. Although for rs10893872, the results showed that there were significant associations in allele model both in pooled analysis and in SLE subgroup. As a conclusion, this meta-analysis demonstrated that these 2 SNPs (rs1128334 and rs10893872) in ETS1 were associated with ADs risk.

Susceptibility of autoimmune diseases in three polymorphisms of infection-associated gene IRAK1.

INTRODUCTION: Infection of pathogenic microorganisms is an important reason for autoimmune diseases (ADs). Interleukin-1 (IL-1) receptor-associated kinase-1 (IRAK1) is a key mediator in infection immunity, while the gene of IRAK1 is recognized as a risk gene in ADs. Three single nucleotide polymorphisms (SNPs) in IRAK1 (rs3027898, rs1059702, rs1059703) are considered to be associated with ADs risk. However, the results are conflicting. We conducted this study to get more precise estimations. METHODOLOGY: PubMed, OvidSP, and CNKI databases (published prior to August 2014) were searched, and data was extracted from eligible studies. The procedure of statistical analysis was performed using STATA 12.0 software. A random effect model or fixed effect model was chosen based on the between-study heterogeneities. RESULTS: Of the studies involved, 11 studies included 10,705 cases (9,865 controls) for rs3027898, 9 studies included 15,005 cases (14,997 controls) for rs1059702, and 7 studies included 8,115 cases (6,815 controls) for rs1059703. Overall, the results showed that there were significant associations with ADs risk in three genetic models for rs3027898 and in four genetic models for rs1059702, but in neither model for rs1059703. Moreover, in stratified analyses, different extents of associations were found in some different genetic models for all three SNPs. CONCLUSION: Our data demonstrated that these three SNPs (rs3027898, rs1059702, rs1059703) in IRAK1 were associated with ADs risk.