Plasmacytoid dendritic cells mediate the tolerogenic effect of CD8+regulatory T cells in a rat tolerant liver transplantation model

BackgroundTolerance is more easily induced in liver transplant models than in other organs; CD8⁺CD45RC^lowregulatory T cells (Tregs) have been shown to induce tolerance in heart allografts. Whether CD8⁺CD45RC^lowTregs could induce tolerance in a liver transplant model and how dendritic cells (DCs) mediate the CD8⁺CD45RC^lowTregs effect remains to be investigated.MethodsA rat liver transplantation model was established and used to test tolerance and acute rejection compared to control groups. Liver function and histopathological changes of allograft were examined by enzyme-linked immunosorbent assay (ELISA) and haematoxylin and eosin (H&E) staining, respectively. The distribution and proportion of CD8⁺CD45RC^lowTregs and plasmacytoid dendritic cells (pDCs) in the allografts and spleen were determined using flow cytometry. Cytokine secretion levels were determined using ELISA and real-time quantitative PCR (qRT-PCR).ResultsThe rat liver transplantation model was well established, with a success rate of 93.3% (28/30). The mean survival time of the tolerant and acute-rejection rats were 156 and 14 days, respectively. The proportions of CD8⁺CD45RC^lowTegs were higher in the allografts of tolerant rats than in those of acute-rejection rats (33.1 ± 4.3 and 12.4 ± 4.6, respectively; P = 0.04). Significant accumulation of pDCs was observed in tolerant liver graft rats compared to that in acute-rejection rats (1.46 ± 0.23 and 0.80 ± 0.20, respectively; P = 0.02). Importantly, CD8⁺CD45RC^lowTregs were positively associated with the frequency of pDCs (P = 0.001, r² = 0.775). The protein and mRNA expression of IL-10 and TGF-β in the allograft group were increased, possibly being responsible for tolerance induction.ConclusionCD8⁺CD45RC^lowT cells interact with pDCs through the induction of IL-10 and TGF-β expression and are responsible for inducing immune tolerance in rat liver transplantation.     

The Lady from Basel’s Barfüsserkirche – Molecular confirmation of the Mummy’s identity through mitochondrial DNA of living relatives spanning 22 generations

The identity of the mummified Lady from the Barfüsser Church in Basel, Switzerland has been unsolved for decades, despite the prominent location of the burial place in front of the choir screen. A recent multidisciplinary research approach came up with a possible candidate, Anna Catharina Bischoff who died in Basel in 1787 with an age of 69 years (1719–1787). To verify the identity of the mummy, genealogists of the Citizen Science Basel discovered three living individuals of the maternal lineage of two different family branches, separated from Anna Catharina Bischoff by up to 22 generations. In this study we compare the ancient mitochondrial DNA of the mummy recovered from a premolar to the mitochondrial DNA of these three candidates. Initially the mitochondrial hypervariable regions I and II of the living individuals were screened using the Sanger sequencing method. This was followed by a mitochondrial capture approach and next generation sequencing to enrich for the whole mitochondrial genome of the mummy and one living person. A full mitochondrial genome has been recovered of both individuals sharing an identical haplotype. The sequence was assigned to the mitochondrial haplogroup U5a1+!16192 including two private mutations 10006G and 16293C. Only by using an interdisciplinary approach combining ancient DNA analysis and genealogy a maternal lineage of a non-noble family spanning 22 generations could be confirmed.     

Passenger lymphocyte syndrome in renal transplantation: A systematic review of published case reports

BackgroundPassenger lymphocyte syndrome (PLS) is an immune-mediated hemolysis that occurs after ABO-mismatched kidney transplantation. PLS is caused by donor lymphocytes producing antibodies to recipient red blood cells, resulting in hemolysis. The incidence of PLS has been reported to be approximately 20% in patients with ABO-mismatched groups. Nevertheless, there is no comprehensive review of PLS following renal transplantation. In this review, we systematically summarized the data of patients with PLS after renal transplantation to help clinicians diagnose and treat more effectively.MethodsA systematic review was conducted using PubMed, Embase, and Web of Science. All relevant data were collected, including age, sex, and clinical and immune parameters.ResultsA total of 91 published cases were identified. The age ranged from 9 to 70 years old and 58.2% were male. Eighty-six cases were only kidney transplantations, one was liver-kidney transplantation, three were pancreas-kidney transplantations, and one was intestinal-kidney transplantation. Of these cases, 27 received kidneys from deceased donors, whereas 40 received kidneys from living donors. Most patients showed immune hemolysis dominated by anaemia, which was significantly improved after symptomatic support treatment, such as blood transfusion and erythropoietin injection.ConclusionPLS is an immune-mediated disease that can occur in patients with ABO-mismatched renal transplantation, which commonly causes hemolysis, although death or deformities of the graft can also occur in patients with the disorder. Symptomatic supportive treatment is an effective treatment scheme at present, but more effective treatment and prevention schemes still need to be explored.     

黄花白及中1个新的苄酯苷类化合物及促凝血活性

目的 对黄花白及Bletilla ochracea块茎的化学成分进行研究。方法 利用硅胶柱色谱、Sephadex LH-20柱色谱、ODS反相柱色谱及HPLC等色谱方法进行分离和纯化，并通过理化性质和波谱数据分析鉴定其结构。采用体外凝血活性评价高含量化合物2和7对活化部分凝血酶时间（activated partial thromboplastin time，APTT）和凝血酶原时间（prothrombin time，PT）的影响。结果 从黄花白及干燥块茎的85%乙醇提取物正丁醇萃取部位中共分离得到了8个苄酯苷类化合物，分别鉴定为1-[4''-β-D-（葡萄糖氧）苄基]-4-{4''-[β-D-葡萄糖氧-（1-2）-β-D-葡萄糖氧）]苄基}-2-异丁基苹果酸酯（1）、1，4-二-[4-（葡萄糖氧）苄基]-2-异丁基苹果酸酯（2）、2-O-葡萄糖基白及苷（3）、手参苷III（4）、4-葡萄糖氧基-肉桂酸葡萄糖氧基苄酯（5）、bleformin J（6）、天麻素（7）、4-羟基苄基-β-D-吡喃葡萄糖苷（8）。化合物2能显著缩短APTT和PT值。结论 其中化合物1为新化合物，命名为黄花白及苷A；化合物3～6和8为首次从该植物分离得到。化合物2具有促凝血活性。     

Combining artificial neural network classification with fully continuous probabilistic genotyping to remove the need for an analytical threshold and electropherogram reading

Standard processing of electrophoretic data within a forensic DNA laboratory is for one (or two) analysts to designate peaks as either artefactual or non-artefactual in a process commonly referred to as profile ‘reading’. Recently, FaSTR™ DNA has been developed to use artificial neural networks to automatically classify fluorescence within an electropherogram as baseline, allele, stutter or pull-up. These classifications are based on probabilities assigned to each timepoint (scan) within the electropherogram. Instead of using the probabilities to assign fluorescence into a category they can be used directly in the profile analysis. This has a number of advantages; increased objectivity in DNA profile processing, the removal for the need for analysts to read profiles, the removal for the need of an analytical threshold. Models within STRmix™ were extended to incorporate the peak label probabilities assigned by FaSTR™ DNA. The performance of the model extensions was tested on a DNA mixture dataset, comprising 2–4 person samples. This dataset was processed in a ‘standard’ manner using an analytical threshold of 50rfu, analyst peak designations and STRmix™ V2.9 models. The same dataset was then processed in an automated manner using no analytical threshold, no analysts reading the profile and using the STRmix™ models extended to incorporate peak label probabilities. Both datasets were compared to the known DNA donors and a set of non-donors. The result between the two processes was a very close performance, but with a large efficiency gain in the 0rfu process. Utilising peak label probabilities opens up the possibility for a range of workflow process efficiency gains, but beyond this allows full use of all data within an electropherogram.     

The association of cognition with protein energy wasting and synaptic transmission in chronic kidney disease

Introduction: In recent years, consciousness impairment in patients with end-stage renal disease (ESRD) has been paid more and more attention, but the cause and mechanism of consciousness state change is not clear. Methods: As the hippocampus played a crucial role in consciousness, we explored the pathological and electrophysiological changes in chronic kidney disease (CKD) mouse hippocampus. Results: Whole-cell recordings in hippocampal neurons showed that miniature excitatory postsynaptic current (mEPSC) frequency decreased, but the amplitude was unaltered in CKD_8w mice. In addition, α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor-mediated EPSCs (AMPAR-EPSCs) and N-methyl-D-aspartic acid receptor-mediated EPSCs (NMDAR-EPSCs) in hippocampal Schaffer collateral-CA1 synapses displayed a significant decline in CKD_8w mice. Although the ratio of AMPAR-/NMDAR-EPSCs did not change, the paired-pulse ratio (PPR) in CKD_8w mice increased. Intriguingly, the mEPSC frequency and AMPAR-/NMDAR-EPSCs amplitudes were positively associated with body weight, and the mEPSC frequency was negatively correlated with serum creatinine in CKD_8w mice, indicating a potential correlation between cognition and nutritional status in patients with CKD. To confirm the above hypothesis, we collected the clinical data from multiple hemodialysis centers to analyze the correlation between cognition and nutritional status. Conclusion: Our analysis indicated that protein energy wasting (PEW) was a possible independent risk factor for consciousness dysfunction in maintenance hemodialysis (MHD) patients. Our results provided a more detailed mechanism underlying the cognitive impairment (CI) in ESRD patients at the synaptic level. Last but not least, our results showed that PEW was a probable new independent risk factor for CI in cases with ESRD.