Probiotic metabolites from Bacillus coagulans GanedenBC30^(TM) support maturation of antigen-presenting cells in vitro

AIM:To study the effects of probiotic metabolites on maturation stage of antigen-presenting immune cells.METHODS:Ganeden Bacillus coagulans 30(GBC30) bacterial cultures in log phase were used to isolate the secreted metabolite(MET) fraction.A second fraction was made to generate a crude cell-wall-enriched fraction,by centrifugation and lysis,followed by washing.A preparation of MET was subjected to size exclusion centrifugation,generating three fractions:< 3 kDa,3-30 kDa,and 30-200 kDa and activities were tested in comparison to crude MET and cell wall in primary cultures of human peripheral blood mononuclear cell(PBMC) as a source of antigen-presenting mononuclear phagocytes.The maturation status of mononuclear phagocytes was evaluated by staining with monoclonal antibodies towards CD14,CD16,CD80 and CD86 and analyzed by flow cytometry.RESULTS:Treatment of PBMC with MET supported maturation of mononuclear phagocytes toward both macrophage and dendritic cell phenotypes.The biological activity unique to the metabolites included a reduction of CD14+ CD16+ pro-inflammatory cells,and this property was associated with the high molecular weight metabolite fraction.Changes were also seen for the dendritic cell maturation markers CD80 and CD86.On CD14dim cells,an increase in both CD80 and CD86 expression was seen,in contrast to a selective increase in CD86 expression on CD14bright cells.The co-expression of CD80 and CD86 indicates effective antigen presentation to T cells and support of T helper cell differentiation.The selective expression of CD86 in the absence of CD80 points to a role in generating T regulatory cells.CONCLUSION:The data show that a primary mechanism of action of GBC30 metabolites involves support of more mature phenotypes of antigen-presenting cells,important for immunological decision-making.

Time-Fractal Modulation—Possible Modulation Effects in Human Therapy

The malignant processes deviate from the healthy homeostatic control, and various “tricks” enable malignant cells to avoid the healthy regulation. Consequently, the malignant structures miss the apoptosis and proliferate without restriction, and without the formation of communication networks in the newly formed cells. The modulation supports the homeostatic control to rearrange the health regulation processes in various ways. The modulation acts with stochastic processes, using stochastic resonances for molecular excitations, supporting the regulative enzymatic processes. The number of stochastic resonant frequencies is as many as the number of enzymatic reactions. The malignant cells differ structurally and dynamically in their connections and interactions from their healthy host tissues. The radiofrequency carrier is modulated with an appropriate time-fractal (1/f) noise to select the autonomic cancer-cells, destroy them, or force the precancerous, semi-individual cells to participate in the networking connections. The modulation in this way limits the cellular autonomy of malignant cells and boosts the healthy control. The resonant energy triggers apoptotic processes and helps immunogenic actions deliver extracellular genetic information for antigen-presentation. The modulation is applied in clinical practice. The therapy (modulated electro-hyperthermia, mEHT) is intensively used in oncology in complementary applications and for palliative stages, and occasionally even as a monotherapy.