Summary Host inflammation alters the availability of nutrients such as iron to limit microbial growth. However, Salmonella enterica serovar Typhimurium thrives in the inflamed gut by scavenging for iron with siderophores. By administering Escherichia coli strain Nissle 1917, which assimilates iron by similar mechanisms, we show that this non-pathogenic bacterium can outcompete and reduce S. Typhimurium colonization in mouse models of acute colitis and chronic persistent infection. This probiotic activity depends on E. coli Nissle iron acquisition as mutants deficient in iron uptake colonize the intestine but do not reduce S. Typhimurium colonization. Additionally, the ability of E. coli Nissle to overcome iron restriction by the host protein lipocalin-2, which counteracts some siderophores, is essential as S. Typhimurium is unaffected by E. coli Nissle in lipocalin-2-deficient mice. Thus, iron availability impacts S. Typhimurium growth and E. coli Nissle reduces S. Typhimurium intestinal colonization by competing for this limiting nutrient.

SUMMARY Amyloid contributes to incapacitating disorders, such as Alzheimer’s disease, by eliciting local inflammation in the brain. However, little is known about how amyloid deposition elicits inflammation. Salmonella enterica serotype Typhimurium produces amyloid-like curli fibrils composed of the protein CsgA. We show that curli fibrils contributed to Nos2 expression in a mouse sepsis model by stimulating Toll-like receptor (TLR) 2. The TLR2 agonist activity of CsgA was markedly reduced by an amino acid substitution (N122A) that also lowered its amyloidogenicity. Synthetic peptides corresponding to residues 111-151 of CsgA or β-amyloid 1-42 from plaques of Alzheimer’s disease stimulated Nos2 production in macrophages and microglia cells through a TLR2-dependent mechanism. This activity was abrogated when a N122A substitution was introduced into the synthetic CsgA peptide. The induction of TLR2-mediated responses by bacterial and eukaryotic amyloids may provide a novel linchpin of pathogenesis, with implications for innate immunity and the immunopathogenesis of Alzheimer’s disease.

Extracellular vesicles (EVs) are nano-sized vesicles, released from many cell types including cardiac cells, have recently emerged as intercellular communication tools in cell dynamics. EVs are an important mediator of signaling within cells that influencing the functional behavior of the target cells. In heart complex, cardiac cells can easily use EVs to transport bioactive molecules such as proteins, lipids, and RNAs to the regulation of neighboring cell function. Cross-talk between intracardiac cells plays pivotal roles in the heart homeostasis and in adaptive responses of the heart to stress. EVs were released by cardiomyocytes under baseline conditions, but stress condition such as hypoxia intensifies secretome capacity. EVs secreted by cardiac progenitor cells and cardiosphere-derived cells could be pinpointed as important mediators of cardioprotection and cardiogenesis. Furthermore, EVs from many different types of stem cells could potentially exert a therapeutic effect on the damaged heart. Recent evidence shows that cardiac-derived EVs are rich in microRNAs, suggesting a key role in the controlling of cellular processes. EVs harboring exosomes may be clinically useful in cell-free therapy approaches and potentially act as prognosis and diagnosis biomarkers of cardiovascular diseases. K E Y W O R D S cardiac cells, cardiovascular disease, exosomes, extracellular vesicles *Jafar Rezaie and Reza Rahbarghazi contributed equally to this work.

The mucosal surfaces are often the first site of interaction between pathogenic microorganisms and the host. Activation of the mucosal immune response has the important function of containing an infection and preventing dissemination of pathogens to systemic sites (barrier function). Numerous lines of evidence suggest that the barrier function is orchestrated by a subset of cytokines (interleukin (IL-)17 and IL-22), which belong to the Th17 family. IL-17 and IL-22 induce expression of antimicrobial peptides and neutrophil chemoattractants at mucosal sites, and thus play an important role in controlling mucosal infections. However, there is increasing evidence that mucosal pathogens achieve greater colonization during inflammation because they are resistant to a subset of these antimicrobial responses. In this review we compare the antimicrobial responses elicited by Th17 cytokines during mucosal infections with four different pathogens: Klebsiella pneumoniae, Citrobacter rodentium, Candida albicans and Salmonella typhimurium. We will then discuss which responses may constitute the mucosal barrier, thus providing a benefit to the host, and which ones may promote the colonization of pathogens, thereby providing a benefit to the microbes.

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BackgroundBreast cancer is the most common malignant in women globally. In Iran, breast cancer incidence rate is continuously increasing. This study aimed to investigate the risk factors for breast cancer in Iranian women.MethodsA hospital-based case-control study was conducted between September 2016 and July 2019 in Arak, Iran. The sample size was 400 breast cancer patients and 400 healthy women. Demographical records and risk factor related data were collected. Logistic regression analysis used to calculate odds ratios (ORs) and 95% confidence intervals (CIs).ResultsData showed that among various factors, urban life (OR = 1.361, 95% CI 1.025–1.808, P = 0.033), height (OR = 3.347, 95% CI 2.0443–5.480, P = 0.000), BMI (OR = 0.397, 95% CI 0.273–0.577, P = 0.000), education level (OR = 7.048, 95% CI 3.985–12.467, P = 0.000), awareness level (OR = 0.507, 95% CI 0.349–0.736, P = 0.000), job status (OR = 0.321, 95% CI 0.122–0.846, P = 0.022), economic status (OR = 4.333, 95% CI 1.424–13.184, P = 0.010), early menarche (OR = 2.815, 95% CI 1.745–4.541, P = 0.000), Stillbirth status (OR = 1.935, 95% CI 1.087–3.446, P = 0.025), family history (OR = 10.281, 95% CI 3.628–29.134, P = 0.000), behavioral habits (OR = 0.554, 95% CI 0.386–0.796, P = 0.001), and second-hand smoking (OR = 1.472, 95% CI 1.108–1.955, P = 0.008) significantly were associated with an increased risk for breast cancer.ConclusionThe data suggest that lifestyle may have more impact on the incidence of breast cancer in Iranian women, suggesting change unhealthy lifestyle and screening for preventing breast cancer.