Active surveillance systems for ARI are superior to passive systems. They should be pathogen-specific and comprehensive for viruses and bacteria and age ranges. They should be population-based and multilevel to avoid bias. The impact of atypical bacteria in children was highly overestimated in earlier studies.

Pathogen reduction (PR) systems for platelets, based on chemically induced cross-linking and inactivation of nucleic acids, potentially prevent transfusion transmission of infectious agents, but can increase clinically significant bleeding in some clinical studies. Here, we documented the effects of PR systems on microRNA and mRNA levels of platelets stored in the blood bank, and assessed their impact on platelet activation and function. Unlike platelets subjected to gamma irradiation or stored in additive solution, platelets treated with Intercept (amotosalen + ultraviolet-A [UVA] light) exhibited significantly reduced levels of 6 of the 11 microRNAs, and 2 of the 3 anti-apoptotic mRNAs (Bcl-xl and Clusterin) that we monitored, compared with platelets stored in plasma. Mirasol (riboflavin + UVB light) treatment of platelets did not produce these effects. PR neither affected platelet microRNA synthesis or function nor induced cross-linking of microRNA-sized endogenous platelet RNA species. However, the reduction in the platelet microRNA levels induced by Intercept correlated with the platelet activation (p < 0.05) and an impaired platelet aggregation response to ADP (p < 0.05). These results suggest that Intercept treatment may induce platelet activation, resulting in the release of microRNAs and mRNAs from platelets. The clinical implications of this reduction in platelet nucleic acids secondary to Intercept remain to be established.

Current treatment for pediatric inflammatory bowel disease (IBD) patients is often ineffective, with serious side effects. Manipulating the gut microbiota via fecal microbiota transplantation (FMT) is an emerging treatment approach but remains controversial. We aimed to assess the composition of the fecal microbiome through a comparison of pediatric IBD patients to their healthy siblings, evaluating risks and prospects for FMT in this setting. A case-control (sibling) study was conducted analyzing fecal samples of six children with Crohn's disease (CD), six children with ulcerative colitis (UC) and 12 healthy siblings by metagenomic sequencing. In addition, lifetime antibiotic intake was retrospectively determined. Species richness and diversity were significantly reduced in UC patients compared with control [Mann-Whitney -test false discovery rate (MWU FDR) = 0.011]. In UC, bacteria positively influencing gut homeostasis, e.g., and , were significantly reduced in abundance (MWU FDR = 0.05). Known pathobionts like were enriched in UC patients (MWU FDR = 0.084). Moreover, abundance correlated positively with that of several virulence genes (SCC> 0.65, FDR < 0.1). A shift toward antibiotic-resistant taxa in both IBD groups distinguished them from controls [MWU Benjamini-Hochberg-Yekutieli procedure (BY) FDR = 0.062 in UC, MWU BY FDR = 0.019 in CD). The collected results confirm a microbial dysbiosis in pediatric UC, and to a lesser extent in CD patients, replicating associations found previously using different methods. Taken together, these observations suggest microbiotal remodeling therapy from family donors, at least for children with UC, as a viable option. In this sibling study, prior reports of microbial dysbiosis in IBD patients from 16S rRNA sequencing was verified using deep shotgun sequencing and augmented with insights into the abundance of bacterial virulence genes and bacterial antibiotic resistance determinants, seen against the background of data on the specific antibiotic intake of each of the study participants. The observed dysbiosis, which distinguishes patients from siblings, highlights such siblings as potential donors for microbiotal remodeling therapy in IBD.

We have reported that cordycepin, an adenosine derivative from the fungus Cordyceps, increased interleukin (IL)-10 expression, decreased IL-2 expression and suppressed T lymphocyte activity. In the present study, we further characterized the regulatory effects of cordycepin on human immune cells. Moreover, a traditional Chinese drug, Cordyceps sinensis (CS) that contains cordycepin, was also investigated. Cytometric Bead Array (CBA) was used to determine the concentrations of IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, TNF-alpha and IFN-gamma in culture of peripheral blood mononuclear cells (PBMCs). The results showed that both cordycepin and CS up-regulated IL-10, IL-1beta, IL-6, IL-8 and TNF-alpha; at the same time, they suppressed phytohemagglutinin (PHA)-induced production of IL-2, IL-4, IL-5, IFN-gamma and IL-12. As compared to cordycepin, CS displayed its regulatory effects on IL-2 and IL-10 in a similar dose-dependent manner even with higher efficiency. The binding activity of transcription factors in a human monocytic cell line THP-1 was tested by the trans-AM method, and a higher binding activity of SP1 and SP3 was observed in cordycepin or CS treated cells compared to the control. These results led to the opinion that cordycepin and CS pleiotropically affected the actions of immune cells and cytokine network in a similar fashion. Cordycepin could be an important immunoregulatory active ingredient in Cordyceps sinensis. In addition, CS may contain substances which possess synergism with cordycepin, as CS showed a higher efficiency in the production of IL-10 and IL-2 than cordycepin. However, merits of these effects in pharmacology and clinical medicine have yet to be proven and the precise mechanism of these immune regulatory actions should be researched.

No abstract