The impact of the micronutrient iodine in health and diseases.

Adequate iodine nutrition is crucial for all mammals by playing his starring role as a component of thyroid hormones, which are key regulators of cellular processes for life such as differentiation, growth, function, and metabolism. Deficiency or excess of iodine in the diet are worldwide highly frequent conditions that are responsible of health problems like hypothyroidism, hypothyroxinemia, goiter, thyroiditis, hyperthyroidism, and autoimmune thyroid diseases among others. The incorporation of iodine in salt or other nutrients resolved the consequences of severe iodine deficiency like goiter, cretinism. However, this strategy in several countries led to other ailments like Hashimoto autoimmune thyroiditis, hyperthyroidism, and hypothyroidism. The goal of this review is to analyze and discuss the different aspects of iodine nutrition for human health comprising its biological role through thyroid hormones, pathogen control, and the regulation of the intestinal microbiota.

Pathogenicity island excision during an infection by Salmonella enterica serovar Enteritidis is required for crossing the intestinal epithelial barrier in mice to cause systemic infection.

Pathogenicity island excision is a phenomenon that occurs in several Salmonella enterica serovars and other members of the family Enterobacteriaceae. ROD21 is an excisable pathogenicity island found in the chromosome of S. Enteritidis, S. Dublin and S. Typhi among others, which contain several genes encoding virulence-associated proteins. Excision of ROD21 may play a role in the ability of S. Enteritidis to cause a systemic infection in mice. Our previous studies have shown that Salmonella strains unable to excise ROD21 display a reduced ability to colonize the liver and spleen. In this work, we determined the kinetics of ROD21 excision in vivo in C57BL/6 mice and its effect on virulence. We quantified bacterial burden and excision frequency in different portions of the digestive tract and internal organs throughout the infection. We observed that the frequency of ROD21 excision was significantly increased in the bacterial population colonizing mesenteric lymph nodes at early stages of the infective cycle, before 48 hours post-infection. In contrast, excision frequency remained very low in the liver and spleen at these stages. Interestingly, excision increased drastically after 48 h post infection, when intestinal re-infection and mortality begun. Moreover, we observed that the inability to excise ROD21 had a negative effect on S. Enteritidis capacity to translocate from the intestine to deeper organs, which correlates with an abnormal transcription of invA in the S. Enteritidis strain unable to excise ROD21. These results suggest that excision of ROD21 is a genetic mechanism required by S. Enteritidis to produce a successful invasion of the intestinal epithelium, a step required to generate systemic infection in mice.

Peripheral Blood Classical Monocytes and Plasma Interleukin 10 Are Associated to Neoadjuvant Chemotherapy Response in Breast Cancer Patients.

Worldwide, breast cancer (BC) is the leading cause of cancer death among women. For many patients the most effective treatment is a resection surgery that removes the tumor. Within this subset, patients sometimes receive chemotherapy treatment (CT) prior to surgery aiming to reduce tumor size in order to preserve healthy breast tissue. This strategy is commonly called neoadjuvant chemotherapy (NAC). This approach also offers an opportunity to determine treatment sensitivity, especially in aggressive tumors. Post NAC absence of residual disease is associated to long term survival in BC patients and is used to define the need of adjuvant therapy options. Studies suggest that NAC allows the recognition of tumor antigens by immune cells potentiating the eradication of the tumor. However, the dynamic changes in patients' immune cells under NAC remain unclear. Here, we assessed changes in leucocyte and cytokine profiles in order to determine its association to NAC response in BC patients. Peripheral blood patient samples were taken prior to each NAC cycle to assess the abundance of leukocyte subsets and serum cytokines in 20 patients. These immunological features were associated with clinical outcomes including pathological response. We found a positive correlation between plasma Interleukin 10 (IL-10) and classical monocytes in HER2+ BC patients under NAC. We also observed a trend between increased IL-10 and classical monocytes levels and lower rates of pathologic complete response at the end of NAC. These data support the notion that monocyte subsets and IL-10 could be applied as a novel indicator of NAC efficacy in HER2+ BC patients. Finally, we confirm a key role of the immune system in cancer progression and CT response.

Heme Oxygenase-1 as a Modulator of Intestinal Inflammation Development and Progression.

Heme Oxygenase 1 (HMOX1) is an enzyme that catalyzes the reaction that degrades the heme group contained in several important proteins, such as hemoglobin, myoglobin, and cytochrome p450. The enzymatic reaction catalyzed by HMOX1 generates Fe2+, biliverdin and CO. It has been shown that HMOX1 activity and the by-product CO can downmodulate the damaging immune response in several models of intestinal inflammation as a result of pharmacological induction of HMOX1 expression and the administration of non-toxic amounts of CO. Inflammatory Bowel Diseases, which includes Crohn's Disease (CD) and Ulcerative Colitis (UC), are one of the most studied ailments associated to HMOX1 effects. However, microbiota imbalances and infections are also important factors influencing the occurrence of acute and chronic intestinal inflammation, where HMOX1 activity may play a major role. As part of this article we discuss the immune modulatory capacity of HMOX1 during IBD, as well during the infections and interactions with the microbiota that contribute to this inflammatory disease.

Comparative and phylogenetic analysis of a novel family of Enterobacteriaceae-associated genomic islands that share a conserved excision/integration module.

Genomic Islands (GIs) are DNA regions acquired through horizontal gene transfer that encode advantageous traits for bacteria. Many GIs harbor genes that encode the molecular machinery required for their excision from the bacterial chromosome. Notably, the excision/integration dynamics of GIs may modulate the virulence of some pathogens. Here, we report a novel family of GIs found in plant and animal Enterobacteriaceae pathogens that share genes with those found in ROD21, a pathogenicity island whose excision is involved in the virulence of Salmonella enterica serovar Enteritidis. In these GIs we identified a conserved set of genes that includes an excision/integration module, suggesting that they are excisable. Indeed, we found that GIs within carbapenem-resistant Klebsiella pneumoniae ST258 KP35 and enteropathogenic Escherichia coli O127:H6 E2348/69 are excised from the bacterial genome. In addition to putative virulence factors, these GIs encode conjugative transfer-related proteins and short and full-length homologues of the global transcriptional regulator H-NS. Phylogenetic analyses suggest that the identified GIs likely originated in phytopathogenic bacteria. Taken together, our findings indicate that these GIs are excisable and may play a role in bacterial interactions with their hosts.

Intestinal Microbiota Influences Non-intestinal Related Autoimmune Diseases.

The human body is colonized by millions of microorganisms named microbiota that interact with our tissues in a cooperative and non-pathogenic manner. These microorganisms are present in the skin, gut, nasal, oral cavities, and genital tract. In fact, it has been described that the microbiota contributes to balancing the immune system to maintain host homeostasis. The gut is a vital organ where microbiota can influence and determine the function of cells of the immune system and contributes to preserve the wellbeing of the individual. Several articles have emphasized the connection between intestinal autoimmune diseases, such as Crohn's disease with dysbiosis or an imbalance in the microbiota composition in the gut. However, little is known about the role of the microbiota in autoimmune pathologies affecting other tissues than the intestine. This article focuses on what is known about the role that gut microbiota can play in the pathogenesis of non-intestinal autoimmune diseases, such as Grave's diseases, multiple sclerosis, type-1 diabetes, systemic lupus erythematosus, psoriasis, schizophrenia, and autism spectrum disorders. Furthermore, we discuss as to how metabolites derived from bacteria could be used as potential therapies for non-intestinal autoimmune diseases.

New insights about excisable pathogenicity islands in Salmonella and their contribution to virulence.

Pathogenicity islands (PAIs) are regions of the chromosome of pathogenic bacteria that harbor virulence genes, which were probably acquired by lateral gene transfer. Several PAIs can excise from the bacterial chromosome by site-specific recombination and in this review have been denominated "excisable PAIs". Here, the characteristic of some of the excisable PAIs from Salmonella enterica and the possible role and impact of the excision process on bacterial virulence is discussed. Understanding the role of PAI excision could provide important insights relative to the emergence, evolution and virulence of pathogenic enterobacteria.