Expansion of Circulating T Follicular Helper Cells in Children with Acute Henoch-Schönlein Purpura

Henoch-Schönlein purpura (HSP) is a common systemic small vessel vasculitis in children with disorder autoimmune responses. T follicular helper (TFH) cells play crucial roles in regulating immune responses. The aim of our study was to investigate the probable role of TFH cells in the pathogenesis of children with HSP. In this study, the frequency of circulating CXCR5+CD4+TFH cells with inducible costimulator (ICOS) expression in the children with acute HSP was significantly higher than that in healthy controls (HCs) but not CXCR5+CD4+TFH cells with programmed death-1 (PD-1) expression. Moreover, serum levels of IL-21 and IL-6 cytokines, IgA, and C3 in HSP children were also significantly higher than those in HCs. A positive correlation was observed between the frequencies of circulating ICOS+CXCR5+CD4+TFH cells and the serum IL-21 or IgA levels of acute HSP children, respectively. Additionally, the mRNA expression levels of interleukin- (IL-) 21, IL-6, and transcriptional factors (B-cell lymphoma-6, Bcl-6) were also significantly increased in peripheral blood from acute HSP children compared to HCs. Taken together, these findings suggest that TFH cells and associated molecules might play critical roles in the pathogenesis of HSP, which are possible therapeutic targets in HSP children

Synthesis and Evaluation of ^99mTc-Labelled 2-Nitroimidazole Derivatives with Different Linkers for Tumour Hypoxia Imaging

When developing novel radiopharmaceuticals, a linker moiety between the chelator and targeting vector can have a crucial influence on adjusting the affinity of the tracer and its biodistribution in organisms. To develop novel 99mTc-labelled hypoxia imaging radiotracers, in this study, five isocyanide-containing 2-nitroimidazole derivatives with different linkers (L1, L2, L3, L4 and L5) were synthesised and radiolabelled with technetium-99m to obtain five stable 99mTc-complexes ([99mTc]Tc-L1, [99mTc]Tc-L2, [99mTc]Tc-L3, [99mTc]Tc-L4 and [99mTc]Tc-L5). Corresponding rhenium analogues of [99mTc]Tc-L1 were synthesised and suggested the structures of these 99mTc-complexes would be a monovalent cation with a technetium (I) core surrounded by six ligands. [99mTc]Tc-L1 is hydrophilic, while the lipophilicities of [99mTc]Tc-L2, [99mTc]Tc-L3, [99mTc]Tc-L4 and [99mTc]Tc-L5 are close. In vitro cell experiments showed that all five novel 99mTc-complexes had higher uptake in hypoxic cells compared with aerobic cells, which indicates the complexes have good hypoxia selectivity. The biodistribution of the five 99mTc-complexes in S180 tumour-bearing mice showed that they all had certain uptake in the tumours. Among them, [99mTc]Tc-L1 had the highest tumour-to-muscle (4.68 ± 0.44) and tumour-to-blood (3.81 ± 0.46) ratios. The introduction of polyethylene glycol (PEG) chains effectively reduced the lipophilicity and decreased uptake by the liver, intestine and blood but also increased clearance from the tumours. In vivo metabolic studies showed [99mTc]Tc-L1 kept intact and remained stable in tumour, blood and urine at 2 h post-injection. The results of SPECT imaging showed that [99mTc]Tc-L1 had significant tumour uptake at 2 h post-injection, but there was still high uptake in abdominal organs such as the liver and kidney, suggesting that this complex needs to be further optimised before being used for tumour hypoxia imaging

Effect of dexamethasone on levels of inflammatory factors and EGF mRNA in rabbits suffering from oral ulcers

Purpose: To investigate the therapeutic effect of dexamethasone on rabbits suffering from oral ulcers, and the underlying mechanism(s) of action. Methods: A rabbit model of oral ulcer was established by applying 40 % glacial acetic acid solution to the oral buccal membranes of the animals. Three groups of rabbits were used. Changes in area of the oral ulcer were recorded after dexamethasone administration. Levels of epidermal growth factor (EGF) were assayed using reverse transcription PCR (RT-PCR), while MDA levels and expression levels of IL- 6, IL-8 and TNF-α were determined by enzyme-linked immunosorbent assay (ELISA). Local histopathological changes were examined histologically with the aid of hematoxylin and eosin (H & E) staining. Results: There were reductions in ulcer areas in group C on the 2nd, 4th and 7th days of dexamethasone administration, when compared with group B (p < 0.05). The EGF levels in the buccal mucosa of rabbits in groups B and C were significantly higher than those in group A (p < 0.05), while the highest EGF level was in group C (p < 0.05). The levels of MDA, IL-6, IL-8, and TNF-α significantly increased in groups B and C (p < 0.05). Results from H & E staining showed lower levels of inflammatory cells in group C than in group B, with visible proliferation of fibroblast cells and epithelial cells in group C after dexamethasone administration. Conclusion: Dexamethasone accelerates healing of oral ulcer by regulating EGF levels. This finding provides a new approach to the treatment of oral ulcers

Molecular epidemiology and genomic characterization of a plasmid-mediated mcr-10 and blaNDM-1 co-harboring multidrug-resistant Enterobacter asburiae

Colistin is considered as one of the last-resort antimicrobial agents for treating multidrug-resistant bacterial infections. Multidrug-resistant E. asburiae has been increasingly isolated from clinical patients, which posed a great challenge for antibacterial treatment. This study aimed to report a mcr-10 and blaNDM-1 co-carrying E. asburiae clinical isolate 5549 conferred a high-level resistance against colistin. Antibiotic susceptibility testing was performed using the microdilution broth method. Transferability of mcr-10 and blaNDM-1-carrying plasmids were investigated by conjugation experiments. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was used to identify modifications in lipid A. Whole genome sequencing and phylogenetic analysis between strain 5549 and a total of 301 E. asburiae genomes retrieved from NCBI database were performed. The genetic characteristics of mcr-10 and blaNDM-1-bearing plasmids were also analyzed. Our study indicated that strain 5549 showed extensively antibiotic-resistant trait, including colistin and carbapenem resistance. The mcr-10 and blaNDM-1 were carried by IncFIB/IncFII type p5549_mcr-10 (159417 bp) and IncN type p5549_NDM-1 (63489 bp), respectively. Conjugation assays identified that only the blaNDM-1-carrying plasmid could be successfully transferred to E. coli J53. Interestingly, mcr-10 did not mediate colistin resistance when it was cloned into E. coli DH5α. Mass spectrometry analysis showed the lipid A palmitoylation of the C-lacyl-oxo-acyl chain to the chemical structure of lipid A at m/z 2063 in strain 5549. In summary, this study is the first to report a mcr-10 and blaNDM-1 co-occurrence E. asburiae recovered from China. Our investigation revealed the distribution of different clonal lineage of E. asburiae with epidemiology perspective and the underlying mechanisms of colistin resistance. Active surveillance is necessary to control the further dissemination of multidrug-resistant E. asburiae

An investigation into mechanism of cation adsorption by reconstruction of calcined layered double hydroxide

Highlights •Mechanism and limit of bivalent-cation adsorption by CHT were investigated. •Half of Mg2+ in CHT was exchangeable independent of the initial Mg2+/Al3+ ratio. •Mg2+ linked to tetrahedral Al3+ in CHT accounted for the exchangeable cation. •Saturated Mg2+/Zn2+ and Mg2+/Ni2+ were close to 1:1 in the reconstructed LDH. •The conclusion was helpful in designing LDH-derived adsorbent and catalyst. Abstract This work investigated the mechanism and limit of cation adsorption by reconstruction of calcined layered double hydroxide (CHT) for the first time. MgxAl-CHT was used to adsorb Zn2+ and Ni2+ from aqueous solution. As a result, adsorption amount of cation was approximately equal to dissolved amount of Mg2+ from CHT. In other words, the molar ratio was close to 1:1 between exchanged cation (Zn2+ or Ni2+) and released Mg2+. Besides, Zn2+ adsorption and Mg2+ dissolution took place synchronously until equilibrium. XRD and SEM indicated that CHT rebuilt layered double hydroxide (LDH) after adsorbing Zn2+ and Ni2+. Furthermore, molar ratios of Mg2+/Zn2+ and Mg2+/Ni2+ were 1:1 in reconstructed CHT regardless of the original Mg2+/Al3+ ratio. Based on these results, it was proposed that half of octahedral Al3+ in LDH transformed into tetrahedral ones after calcination, resulting in half of Mg2+ bond being distorted in CHT and ready for a potential exchange. When CHT was used to adsorb bivalent cation (Me2+), the maximum amount of adsorption was the half amount of Mg2+, and MgMeAl-LDH was formed by dissociation-deposition