Liver graft injury caused by de novo donor-specific HLA antibodies in pediatric liver transplant recipients with low, moderate, and high immunologic risk.

BACKGROUND: This study investigated the association between different risk levels of de novo donor-specific anti-human leukocyte antigen antibodies (dnDSAs) and liver graft injury after liver transplantation in pediatric patients. METHODS: This retrospective cohort study enrolled 130 patients after liver transplantation. Subjects were divided into the following 4 groups according to the mean fluorescence intensity (MFI) of dnDSAs: high risk group(MFI ≥10,000), medium risk group(4000 ≤ MFI <10,000), low risk group(500 ≤ MFI <4000), and negative group(<500). Liver function indices were examined along with liver puncture biopsy，and the relationship between dnDSA risk level and liver injury after transplantation was assessed. RESULTS: Pediatric liver transplant recipients showed significant differences in liver function (ALT, AST, GGT and Bilirubin) according to dnDSA risk level (P < 0.05), and no differences in cumulative incidences of rejection (P = 0.413) and liver fibrosis (P = 0.978) were observed among the number of dnDSAs group. There were differences in the cumulative incidences of antibody-mediated rejection (AMR) (P = 0.001) and T cell-mediated rejection （TCMR） (P = 0.003) across risk groups. The cumulative incidences of TCMR and liver fibrosis (P = 0.0001) were higher in the low-risk group than in the other 3 groups. There were no differences in graft survival rate (P = 0.846) across risk groups. CONCLUSION: DnDSAs in pediatric liver transplant recipients are associated with liver transplant rejection and fibrosis. The level of dnDSAs in low risk group should not be disregarded. Routine detection of dnDSAs has clinical utility for noninvasive risk stratification in this population.

Development of ecological risk assessment for Diisobutyl phthalate and di-n-octyl phthalate in surface water of China based on species sensitivity distribution model.

Phthalic acid esters (PAEs) are commonly used as plasticizer and are emerging concern worldwide for potent adverse effects of aquatic organisms. Certain PAEs were often detected in different environmental matrices but related toxicity data were still lacking to support their risk assessment. The study investigated the acute toxicity of Diisobutyl phthalate (DiBP) and Di-n-octyl phthalate (DnOP) using 6 Chinese resident aquatic organisms from 3 phyla and 6 species and constructed the species sensitivity distribution (SSD) models for ecological risk assessment. Lethal concentration 50% (LC50) ranges of DiBP and DnOP were 4.89-21.45 mg/L and 1.45-1200 mg/L, respectively. The derived acute and chronic predicted no-effect concentrations (PNECs) based on log-normal model of water were 0.54 and 0.04 mg/L for DiBP and 0.23 and 0.05 mg/L for DnOP, respectively. The ERA for DiBP and DnOP in the surface water and sediment of China was conducted. Water samples of Haihe Rive (RQ = 0.41) and Hun River (RQ = 0.16) of DiBP showed medium risk. And sediment samples of Yellow River (RQ = 0.71) and Chao Hu Lake (RQ = 0.42) of DiBP showed medium risk. Meanwhile, the above water and sediment samples (RQ＜0.1) of DnOP showed low risk.

Clinical relevance of donor-specific human leukocyte antigen antibodies after pediatric liver transplantation.

Donor-specific human leukocyte antigen (HLA) antibodies (DSAs) have a significant role in graft survival after pediatric liver transplantation. To understand the significance of DSAs, a retrospective cohort study of 48 pediatric liver transplant recipients with posttransplant serum samples that were analyzed for DSAs was performed. According to their test results, the recipients were divided into a DSA-positive group and a DSA-negative group. Postoperative liver transplantation biopsies were performed in patients with abnormal liver function. The liver condition and prognosis of the recipients were recorded, and their association was analyzed. A total of 48 recipients were followed up for 2.7±0.8 years. DSA positivity was detected in 10 cases (20.8%). One case was positive for HLA class I and HLA class II antibodies, whereas 9 cases were positive for HLA class II antibodies, and the gene loci were HLA-DR and/or DQ. Antibody-mediated rejection (AMR) occurred in four of 10 patients in the DSA-positive group. Liver function was abnormal in 3 of 38 cases in the DSA-negative group. Multivariate analysis revealed that DSA positivity was an independent risk factor for liver insufficiency and long-term survival of recipients. In addition, Kaplan-Meier survival analysis demonstrated that there were significant differences in the survival of graft recipients between the DSA-positive group and the DSA-negative group (P<0.05). The positivity of DSAs after pediatric liver transplantation was closely related to the occurrence of AMR. These results suggested that DSAs should be routinely monitored post-operatively, and that DSA-positive recipients should be screened as soon as possible and given appropriate treatment.

De novo donor-specific HLA antibodies reduce graft survival rates and increase the risk of kidney transplant rejection: A single-center retrospective study.

BACKGROUND: We investigated the impact of de novo donor-specific anti-human leukocyte antigen antibodies (dnDSAs) on long-term death-censored graft survival and renal allograft rejection in kidney transplant recipients. METHODS: The sample for this retrospective cohort study comprised 121 recipients of kidney transplants with negative complement-dependent cytotoxicity crossmatches to their deceased donors. Recipients were divided into two groups: dnDSAs+ (n = 31) and dnDSAs- (n = 90). We evaluated rejection and long-term graft survival rates in the recipients along with pathologic changes in the transplanted kidneys. RESULTS: DnDSAs were identified in 31/121 patients (25.6%). The graft survival rate in the dnDSAs+ group was 87.1% (27/31) and that of the dnDSAs- group was 97.8% (88/90). The dnDSAs+ group had lower graft survival rates than patients without dnDSAs (p = 0.007). There was no difference in the graft survival rates between patients with high DSA mean fluorescence intensity (≥4000) and those with low intensity (<4000) (p = 0.669). There was also no difference in the graft survival rates of patients with HLA class I, II, and I + II dnDSAs (p = 0.571). The presence of dnDSA in serum was associated with a higher incidence of antibody- and T-cell-mediated rejection (p < 0.0001). Banff scores for arterial fibrointimal and arteriolar hyalin, thickening as well as C4d deposition differed for the dnDSAs+ and dnDSAs- groups (p < 0.05). CONCLUSION: DnDSAs were found to be associated with decreased long-term graft survival rates and increased rejection rates, often accompanied by C4d deposition.

Modelling the kinetics of aggregate breakage using improved breakage kernel.

An improved breakage kernel was developed to describe the kinetics of aggregate breakage induced by fluid shear. The model includes the effects of both the internal bonding forces of an aggregate and the fluid shear stress exerting on the aggregate. The ratio of the two opposite forces regulates the probability of the aggregate breakage. With the improved breakage model and the sectional numerical technique, the breakage dominant process can be well simulated by the change in particle size distribution (PSD). The results show that the fractal dimension plays a significant role in the breakage process. As the fractal dimension approaches three, the aggregates become more difficult to break. Higher shear intensity, to a great extent, enhances the breakage kinetics. The internal forces are directly related to the bonding strength of the aggregates. Hydrophobic forces increase the floc strength and hence reduce the breakage rate and probability. In addition, two distinct breakage daughter distribution functions, binary and ternary, give eventually almost the same results in PSD after breakage. It appears that the breakage daughter distribution function is less important for the description of the particle fragmentation.

Quercetin enhances the effects of 5-fluorouracil-mediated growth inhibition and apoptosis of esophageal cancer cells by inhibiting NF-κB.

Despite its limited success, 5-fluorouracil (5-FU) remains the primary chemotherapy agent for the treatment of esophageal cancer. Quercetin has been demonstrated to inhibit the growth of transformed cells. The present study was conducted to examine whether quercetin combined with conventional chemotherapeutic agents would improve the therapeutic strategy for esophageal cancer. In this study, an MTT assay was used to determine the effects of quercetin on the proliferation of EC9706 and Eca109 cells. Annexin V-FITC/propidium iodide (PI)-stained fluorescence-activated cell sorter (FACS) analysis was used to detect the apoptotic fraction of treated cells, and western blot analysis was used to examine the protein levels. The results of our study demonstrated that quercetin in combination with 5-FU significantly inhibited growth (P<0.05) and stimulated apoptosis (P<0.005) in EC9706 and Eca109 esophageal cancer cells compared with quercetin or 5-FU alone. These changes were associated with the decreased expression of a phosphorylated inhibitory molecule of NF-κB (pIκBα), which was activated by exposure to 5-FU alone. We suggest that inclusion of quercetin to the conventional chemotherapeutic agent 5-FU may be an effective therapeutic strategy for esophageal cancer.

Neuroprotective mechanism of modafinil on Parkinson disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.

AIM: To observe the neuroprotective mechanism of modafinil on Parkinson disease (PD) models induced by 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP). METHODS: The model of PD was induced by intraperitoneally injecting MPTP into C57BL/6J mice for 4 d. Modafinil (i.p., 50 or 100 mg/kg(-1)/d(-1)) was administered at 30 min following MPTP for 4 d and for another 10 d continuously. The contents of dopamine (DA), noradrenaline (NA), 5-hydroxytryptamine (5-HT), gamma-aminobutyric acid (GABA), glutamine (Glu) in the striatum, and the contents of GABA, Glu, malondialdehyde (MDA), and glutathione (GSH) in the substantia nigra (SN) of model mice were determined. RESULTS: Modafinil (50 and 100 mg/kg) prevented against the decrease of the contents of DA, 5-HT, and NA in the striatum and GSH, GABA in the SN induced by MPTP, but reduced the increase of MDA in the SN and GABA in the striatum induced by MPTP. Modafinil preferentially inhibited striatal GABA release, but it did not change the increase of nigrostriatal Glu release induced by MPTP. CONCLUSION: The anti-oxidation and the modulation of nigrostriatal GABA and striatal NA and 5-HT release contributed to the neuroprotective effects of modafinil on PD induced by MPTP.