Background: Carbonic anhydrase (CA) isozymes may have an important role in cancer development. Some isozymes control pH homeostasis in tumors that appears to modulate the behaviour of cancer cells. CA XIII is the newest member of the CA gene family. It is a cytosolic isozyme which is expressed in a number of normal tissues. The present study was designed to investigate CA XIII expression in prospectively collected colorectal tumor samples. Methods: Both neoplastic and normal tissue specimens were obtained from the same patients. The analyses were performed using CA XIII-specific antibodies and an immunohistochemical staining method. For comparison, the tissue sections were immunostained for other cytosolic isozymes, CA I and II. Results: The results indicated that the expression of CA XIII is down-regulated in tumor cells compared to the normal tissue. The lowest signal was detected in carcinoma samples. This pattern of expression was quite parallel for CA I and II. Conclusion: The down-regulation of cytosolic CA I, II and XIII in colorectal cancer may result from reduced levels of a common transcription factor or loss of closely linked CA1, CA2 and CA13 alleles on chromosome 8. Their possible role as tumor suppressors should be further evaluated.

Immunosenescence, i.e. the aging-associated decline of the capacity of the immune system, is characterized by several distinct changes in the number and functions of the immune cells. In the case of B cells, the total number of CD19+ B cells is lower in the blood of elderly individuals than in the younger ones. CD19+ B cell population contains several subsets, which are commonly characterized by the presence of CD27 and IgD molecules, i.e. naïve B cells (CD27- IgD+), IgM memory (CD27+ IgD+), switched memory (CD27+ IgD-) and late memory (CD27- IgD-). This late memory, double negative, population represents cells which are nondividing, but are still able to produce inflammatory mediators and in this way maybe contributing to the aging-associated inflammation, inflammaging. Here we have focused on the role of these B cell subsets in elderly individuals, nonagenarians, in the regulation of inflammation and inflammation-associated decline of bodily functions. As the biological aging process demonstrates gender-specific characteristics, the analyses were performed separately in males and female. A subcohort of The Vitality 90+ study (67 nonagenarians, 22/45 males/females and 40 young controls, 13/27 males/females) was used. Flow cytometric analysis indicated that the total percentage of the CD19+ cells was ca. 50% lower in the nonagenarians than in the controls in both genders. The proportions of these four B cell subsets within the CD19+ populations were very similar in young and old individuals. Thus, it seems that the aging-associated decline of the total CD19+ cells affects similarly all these B cell subsets. To analyze the role of these subsets in the regulation of inflammation, the correlation with IL-6 levels was calculated. A significant correlation was observed only with the percentage of CD27- IgD- cells and only in males. As inflammation is associated with aging-associated functional performance and frailty, the correlations with the Barthel index and frailty score was analyzed. Again, only the CD27- IgD- population demonstrated a strong male-specific correlation. These data show that the CD27- IgD- B cell subset demonstrates a strong pro-inflammatory effect in nonagenarians, which significantly associates with the decline of the bodily functions. However, this phenomenon is only observed in males.

According to the hygiene and biodiversity hypotheses, frequent exposure to environmental microbiota, especially through soil contact, diversifies commensal microbiota, enhances immune modulation, and ultimately lowers the risk of immune-mediated diseases. Here we test the underlying assumption of the hygiene and biodiversity hypotheses by instructing volunteers to grow edible plants indoors during the winter season when natural exposure to environmental microbiota is low. The one-month randomized, placebo-controlled double-blind trial consisted of two treatments: participants received either microbially diverse growing medium or visually similar but microbially poor growing medium. Skin microbiota and a panel of seven immune markers were analyzed in the beginning of the trial and after one month. The diversity of five bacterial phyla (Bacteroidetes, Planctomycetes, Proteobacteria, Cyanobacteria, and Verrucomicrobia) and one class (Bacteroidia) increased on the skin of participants in the intervention group while no changes were observed in the placebo group. The number of nodes and edges in the co-occurrence networks of the skin bacteria increased on average three times more in the intervention group than in the placebo group. The plasma levels of the immunomodulatory cytokine interleukin 10 (IL-10) increased in the intervention group when compared with the placebo group. A similar trend was observed in the interleukin 17A (IL-17A) levels and in the IL-10:IL-17A ratios. Participants in both groups reported high satisfaction and adherence to the trial. The current study provides evidence in support of the core assumption of the hygiene and biodiversity hypotheses of immune-mediated diseases. Indoor urban gardening offers a meaningful and convenient approach for increasing year-round exposure to environmental microbiota, paving the way for other prophylactic practices that might help prevent immune-mediated diseases.

Introduction: The hygiene hypothesis suggests that decrease in early life infections due to increased societal‐level hygiene standards subjects one to allergic and autoimmune diseases. In this report, we have studied the effect of sterilized forest soil and plant‐based material on mouse immune system and gut microbiome.Methods: Inbred C57Bl/6 mice maintained in normal sterile environment were subjected to autoclaved forest soil‐derived powder in their bedding for 1 h a day for 3 weeks. Immune response was measured by immune cell flow cytometry, serum cytokine enzyme‐linked immunoassay (ELISA) and quantitative polymerase chain reaction (qPCR) analysis. Furthermore, the mouse gut microbiome was analyzed by sequencing.Results: When compared to control mice, mice treated with soil‐derived powder had decreased level of pro‐inflammatory cytokines namely interleukin (IL)−17F and IL‐21 in the serum. Furthermore, splenocytes from mice treated with soil‐derived powder expressed less IL‐1b, IL‐5, IL‐6, IL‐13, and tumor necrosis factor (TNF) upon cell activation. Gut microbiome appeared to be stabilized by the treatment.Conclusions: These results provide insights on the effect of biodiversity on murine immune system in sterile environment. Subjecting mice to soil‐based plant and microbe structures appears to elicit immune response that could be beneficial, for example, in type 2 inflammation‐related diseases, that is, allergic diseases.

Type 2 inflammation‒related cytokine IL-13 plays a protective role in experimental papilloma induction in mice. To understand the mechanisms by which IL-13 contributes to papilloma formation, we utilized Il13rα1-knockout (KO) mice in a widely used 7,12-dimethylbenz[a]anthracene/12-O-tetradecanoyl phorbol-13-acetate two-stage skin carcinogenesis protocol that mimics the development of squamous cell carcinoma. KO mice developed more papillomas and significantly faster than wild-type mice. Papilloma development reduced regulatory T cells in wild-type mice but substantially less in KO mice. In line with this, IL-2 and IL-10 levels decreased in wild-type mice but not in KO mice. Furthermore, systemic IL-5 and TSLP levels were elevated, whereas IL-22 was decreased during papilloma formation in the skin of KO mice. Polymorphonuclear myeloid‒derived suppressor cells were decreased in the KO mice at the early phase of papilloma induction. We show that IL-13Rα1 protects from papilloma development in chemically induced skin carcinogenesis, and our results provide further insights into the protective role of functional IL-4 and IL-13 signaling through type II IL-4 receptor in tumor development.