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Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest.

The gut microbiota is a considerable source of biologically active compounds that can promote intestinal homeostasis and improve immune responses. Here, we used large expression libraries of cloned metagenomic DNA to identify compounds able to sustain an anti-inflammatory reaction on host cells. Starting with a screen for NF-κB activation, we have identified overlapping clones harbouring a heterodimeric ATP-binding cassette (ABC)-transporter from a Firmicutes. Extensive purification of the clone's supernatant demonstrates that the ABC-transporter allows for the efficient extracellular accumulation of three muropeptide precursor, with anti-inflammatory properties. They induce IL-10 secretion from human monocyte-derived dendritic cells and proved effective in reducing AIEC LF82 epithelial damage and IL-8 secretion in human intestinal resections. In addition, treatment with supernatants containing the muropeptide precursor reduces body weight loss and improves histological parameters in Dextran Sulfate Sodium (DSS)-treated mice. Until now, the source of peptidoglycan fragments was shown to come from the natural turnover of the peptidoglycan layer by endogenous peptidoglycan hydrolases. This is a report showing an ABC-transporter as a natural source of secreted muropeptide precursor and as an indirect player in epithelial barrier strengthening. The mechanism described here might represent an important component of the host immune homeostasis., Competing Interests: Competing interests statement:M.N., J.D., H.M.B., A.C., and C. Bonny are the inventors of a patent application protecting the heterodimeric transporter (WO 2021/​148661). The other authors have no conflicts of interest to declare aside from the fact that several of the authors are employees of private companies.

This study focuses on the synthesis of 1,7- and 3,4-indole-fused lactones via a simple and efficient reaction sequence. The functionalization of these "oxazepino-indole" and "oxepino-indole" tricycles is carried out by palladium catalysed CC coupling, nucleophilic substitution or 1,3-dipolar cycloaddition. The evaluation of their activity against Mycobacterium tuberculosis shows that the "oxazepino-indole" structure is a new inhibitor of M. tuberculosis growth in vitro., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Progression of prostate cancer to androgen independence remains the primary obstacle to improved survival. The development of more effective treatments depends on our understanding of the molecular events associated with the hormone-refractory stage. We quantified, among 90 screened genes, the expression of 37 target genes, using real-time quantitative RT-PCR. Gene expression was studied in 13 samples of HPRC compared to 33 clinically localised cancers and normal prostate tissue. We identify 19 genes with significant differential expression in HRPC compared to localised prostate cancer. Genes with decreased expression included receptors for growth factors, MMR genes and the serine protease hepsin. Analysis of increased gene expression confirmed the importance of AR upregulation and highlighted genes not previously linked to HRPC, including enzymes involved in steroid synthesis and the antiapoptotic factor survivin. Progression of prostate cancer to the hormone-refractory state is associated with differential gene expression, which may prove useful for both understanding disease progression and the development of new therapeutic approaches., ((c) 2004 Wiley-Liss, Inc.)

Purpose: Benign prostatic hyperplasia (BPH) is characterized by a hyperplastic growth of epithelial and stromal cells in the prostate. Despite the high prevalence of the disease little is known regarding the molecular etiology of BPH. Therefore, a comparison of gene expression patterns between normal prostate, BPH and prostate cancer could provide insights into the pathogenic mechanisms of the disease and identify candidate genes that could be targeted for therapeutic use., Materials and Methods: Prostate tissue specimen were obtained from 30 patients undergoing adenomectomy for BPH. Adenoma weight was less than 60 gm in 15 patients and more than 60 gm in the remainder. Normal prostate tissue was obtained from 15 patients undergoing radical prostatectomy for cancer from areas selected for absent tumor and BPH. Two pools of organ confined prostate cancer were also analyzed. We quantified in the 5 pools of tissues the expression of 327 genes using real-time quantitative reverse transcriptase-polymerase chain reaction., Results: A total of 23 genes showed increased expression in BPH with a fold change of at least 2.5 between normal prostate and the 2 BPH groups, of which most were normal or down-regulated in prostate cancer. Seven genes showed decreased expression in BPH with a fold change of at least 3.5 between normal prostate and BPH. Most of them were also normal or down-regulated in prostate cancer., Conclusions: We identified a set of genes up-regulated in BPH compared to normal prostate tissue and often prostate cancer, including genes previously implicated in BPH and others not previously linked to this disease to our knowledge. Further investigations are now warranted to determine the clinical relevance and therapeutic potential of these genes.

To address the question of how many distinct parasites are injected when a mosquito bites, we have characterized isolates resulting most probably from a single sporozoite inoculum. We describe the direct and immediate cloning on hepatocyte feeder layers of a Thai and an African Plasmodium falciparum primary isolate and the characterization of 67 independent clones by four techniques totaling nine different markers. This led to three main conclusions: (a) both the phenotypic and genotypic markers revealed an unexpectedly large degree of diversity within the clones from a single isolate; (b) the clones are nonetheless genetically related; and (c) a single mosquito inoculum would most likely be sufficient to generate considerable isolate complexity in the absence of repeated exposure. This diversity, which has been greatly underestimated in previous studies, does not bode well for the development of successful malaria control means.