In some diseases, a very important role is played by the ability of bacteria to form multi-dimensional complex structure known as biofilm. The most common disease of the oral cavity, known as dental caries, is a top leader. Streptococcus mutans, one of the many etiological factors of dental caries, is a microorganism which is able to acquire new properties allowing for the expression of pathogenicity determinants determining its virulence in specific environmental conditions. Through the mechanism of adhesion to a solid surface, S. mutans is capable of colonizing the oral cavity and also of forming bacterial biofilm. Additional properties enabling S. mutans to colonize the oral cavity include the ability to survive in an acidic environment and specific interaction with other microorganisms colonizing this ecosystem. This review is an attempt to establish which characteristics associated with biofilm formation—virulence determinants of S. mutans—are responsible for the development of dental caries. In order to extend the knowledge of the nature of Streptococcus infections, an attempt to face the following problems will be made: Biofilm formation as a complex process of protein–bacterium interaction. To what extent do microorganisms of the cariogenic flora exemplified by S. mutans differ in virulence determinants “expression” from microorganisms of physiological flora? How does the environment of the oral cavity and its microorganisms affect the biofilm formation of dominant species? How do selected inhibitors affect the biofilm formation of cariogenic microorganisms?

The importance of monocyte chemotactic protein-1-induced protein 1 (MCPIP1) in the negative regulation of inflammatory reactions has already been extensively studied. However, its role in cancer is not yet established. We studied MCPIP1 gene expression in primary human neuroblastomas and several neuroblastoma cell lines. Our results showed a lack of MCPIP1 expression in primary neuroblastoma tumors. Moreover, it was found that the low expression of the protein measured in human neuroblastoma cell lines might be important for neuroblastoma survival, since enforced MCPIP1 gene expression in human neuroblastoma BE(2)-C cells caused a significant decrease in neuroblastoma cell viability and proliferation.

The protein p53 protects the organism against carcinogenic events by the induction of cell cycle arrest and DNA repair program upon DNA damage. Virtually all cancers inactivate p53 either by mutations/deletions of the TP53 gene or by boosting negative regulation of p53 activity. The overexpression of MDM2 protein is one of the most common mechanisms utilized by p53wt cancers to keep p53 inactive. Inhibition of MDM2 action by its antagonists has proved its anticancer potential in vitro and is now tested in clinical trials. However, the prolonged treatment of p53wt cells with MDM2 antagonists leads to the development of secondary resistance, as shown first for Nutlin-3a, and later for three other small molecules. In the present study, we show that secondary resistance occurs also after treatment of p53wt cells with idasanutlin (RG7388, RO5503781), which is the only MDM2 antagonist that has passed phase II and entered phase III clinical trials, so far. Idasanutlin strongly activates p53, as evidenced by the induction of p21 expression and potent cell cycle arrest in all the three cell lines tested, i.e., MCF-7, U-2 OS, and SJSA-1. Notably, apoptosis was induced only in SJSA-1 cells, while MCF-7 and U-2 OS cells were able to restore the proliferation upon the removal of idasanutlin. Moreover, idasanutlin-treated U-2 OS cells could be cultured for long time periods in the presence of the drug. This prolonged treatment led to the generation of p53-mutated resistant cell populations. This resistance was generated de novo, as evidenced by the utilization of monoclonal U-2 OS subpopulations. Thus, although idasanutlin presents much improved activities compared to its precursor, it displays the similar weaknesses, which are limited elimination of cancer cells and the generation of p53-mutated drug-resistant subpopulations.

Our results indicate that the high levels of antioxidants in saliva increase significantly in children in line with the salivary cariogenic bacterial profiles and caries progression.

Accumulation of neutrophils in the site of inflammation is a typical mechanism of innate immunity. The accumulated neutrophils are exposed to stressogenic factors usually associated with inflammation. Here, we studied response of human peripheral blood neutrophils subjected to short, febrile-range heat stress. We show that 90 min heat stress slowed down the spontaneous apoptosis of neutrophils. In the absence of typical markers of apoptosis the heat-shocked neutrophils induced antiinflammatory effect in human monocyte-derived macrophages (hMDMs), yet without being engulfed. Importantly, the expression of FcγRIII (CD16) was sharply reduced. Surprisingly, concentration of the soluble CD16 did not change in heat-shocked neutrophil supernates indicating that the reduction of the cell surface CD16 was achieved mainly by inhibition of fresh CD16 delivery. Inhibitors of 90 kDa heat shock protein (HSP90), a molecular chaperone found in membrane platforms together with CD16 and CD11b, significantly increased the observed effects caused by heat shock. The presented data suggest a novel systemic aspect of increased temperature which relies on immediate modification by heat of a neutrophil molecular pattern. This effect precedes cell death and may be beneficial in the initial phase of inflammation providing a nonphlogistic signal to macrophages before it comes from apoptotic cells.

BackgroundStreptococcus mutans is known to be a primary etiological factor of dental caries, a widespread and growing disease in Polish children. Recognition of novel features determining the pathogenicity of this pathogen may contribute to understanding the mechanisms of bacterial infections.The goal of the study was to determine the activity of prephenate dehydrogenase (PHD) and to illuminate the role of the enzyme in S. mutans pathogenicity. The strains were biotyped based on STREPTOtest 24 biochemical identification tests and the usefulness of biotyping in the determination of S. mutans pathogenicity determinants was examined.ResultsOut of ninety strains isolated from children with deciduous teeth fifty three were classified as S. mutans species. PDH activity was higher (21.69 U/mg on average) in the experimental group compared to the control group (5.74 U/mg on average) (P <0.001). Moreover, it was demonstrated that biotype I, established basing on the biochemical characterization of the strain, was predominant (58.5%) in oral cavity streptococcosis. Its dominance was determined by higher PDH activity compared to biotypes II and III (P = 0.0019).ConclusionsThe usefulness of biotyping in the determination of Streptococcus mutans pathogenicity determinants was demonstrated. The obtained results allow for better differentiation of S. mutans species and thus may contribute to recognition of pathogenic bacteria transmission mechanisms and facilitate treatment.

PurposeOur insight in the genetics of Hashimoto’s thyroiditis (HT) has become clearer through information provided by genome-wide association studies and candidate gene studies, but remains still not fully understood. Our aim was to assess how many different genetic risk variants contribute to the development of HT.Methods147 HT cases (10.2% men) and 147 controls (13.6% men) were qualified for the analysis. Intrinsic and environmental factors were controlled for. Polymorphisms (SNP) were chosen based on the literature and included markers of the genes PTPN22, CTLA4, TG, TPO among others, and of genomic regions pointed by GWAS studies. SNP were typed on a microarray. Variants in the HLA-DRB1 gene were identified by Sanger sequencing.ResultsMultivariate predisposition to HT was modeled. Based on the investigated group, a model of seven variables was obtained. The variability explained by this model was assessed at only 5.4821% (p = 2 × 10−6), which indicates that many dozens of factors are required simultaneously to explain HT predisposition.ConclusionsWe analyzed genetic regions commonly and most significantly associated with autoimmune thyroid disorders in the literature, on a carefully selected cohort. Our results indicated a lack of possibility to predict the risk of HT development, even with a multivariate model. We therefore conclude that strong associations of single genetic regions with HT should be interpreted with great caution. We believe that a change in the attitude towards genetic association analyses of HT predisposition is necessary. Studies including multiple factors simultaneously are needed to unravel the intricacies of genetic associations with HT.Electronic supplementary materialThe online version of this article (10.1007/s40618-018-0910-4) contains supplementary material, which is available to authorized users.

An increasing interest in improving the quality of life of patients with autoimmune thyroid disorders has been noted during recent years. Although there is little scientific evidence, many patient-oriented publications, websites and support groups recommend changes in diet as well as nutritional supplement use as a cure for thyroid disease and the mean for ailments reduction. The presented survey aimed to explore the patients’ and medical professionals’ approach to nutritional treatments of AIT. Material and methods. (1) Medical professionals: 30 physicians, 32 nutritionists, 35 medical students and 27 dietetics students responded to an internet questionnaire on the recommendations for a nutritional approach in AIT (gluten-free and lactose-free diet, selenium, vitamin D, and iodine supplementation). (2) AIT patients: 150 subjects aged 18 to 70 years (146 females, 4 males) responded to an internet questionnaire on the nutritional approach in their disease. Questions concerned: gluten-free and lactose-free diet, as well as vitamins and microelements use, the source of the patients’ knowledge, and the recommending body behind their decision on changes in nutrition. Results. (1) Medical professionals. 54% of the surveyed subjects recommended their patients the use of selenium supplements (9.7% in Graves’ ophthalmopathy), 41.3% - iodine supplements, 92.3% -vitamin D supplements. 6.4% of responders advised a gluten-free diet regardless of the coexistence of gluten-related disorders, and 4.8% - a lactose-free diet even in the absence of lactose intolerance. There were discrepancies in recommendations between professionals: physicians advised iodine and selenium least often. (2) AIT patients. 44.3% of responders were on a lactose-free, and 37.3% - on a gluten-free diet. Only 2% of responders were diagnosed with celiac disease. 38% of responders who had modified their diet have decided to do so following the recommendation of a medical professional, the remaining 62% - without any advice. 36.7% of responders were using selenium supplements (27.3% following a physician’s recommendation), 8% - iodine supplements (all advised by a physician), 74.7% - vitamin D supplements (48.7% of them have obtained recommendations). Websites (80.7%) and patients-oriented publications (50.7%) were the main sources of AIT patients’ knowledge and opinions on the role of nutrition in AIT management. Conclusions. AIT patients commonly decide to implement a nutrition-based approach to their disease, even without any professional advice. Although the results of the survey are biased by internet methodology, it is worrying that many medical professionals advise introduction of diets and supplements which have not been proven to be effective and may even be harmful (gluten-free diet) against guidelines of medical societies.