Background Sjögren’s syndrome (SS) is a chronic autoimmune disease primarily characterized by inflammation in the salivary and lacrimal glands. Activated T cells contribute to disease pathogenesis by producing proinflammatory cytokines, which leads to a positive feedback loop establishment. The study aimed to evaluate the effects of secreted factors derived from dental pulp stem cells (DPSCs) or bone marrow mesenchymal stem cells (BMMSCs) on hyposalivation in SS and to investigate the mechanism involved. Methods Eighty percent confluent stem cells were replenished with serum-free Dulbecco’s modified Eagle’s medium and incubated for 48 h; following which, conditioned media from DPSCs (DPSC-CM) and BMMSCs (BMMSC-CM) were collected. Cytokine array analysis was performed to assess the types of cytokines present in the media. Flow cytometric analysis was performed to evaluate the number of activated T cells cultured in DPSC-CM or BMMSC-CM. Subsequently, DPSC-CM or BMMSC-CM was administered to an SS mouse model. The mice were categorized into the following groups (n = 6 each): non-treatment, Dulbecco’s modified Eagle’s medium (−), BMMSC-CM, and DPSC-CM. Histological analysis of the salivary glands was performed. The gene and protein expression levels of cytokines associated with T helper subsets in the submandibular glands (SMGs) were evaluated. Results DPSC-CM contained more secreted factors with tissue-regenerating mechanisms, such as cell proliferation, anti-inflammatory effects, and immunomodulatory effects. DPSC-CM was more effective in suppressing the activated T cells than other groups in the flow cytometric analysis. The stimulated salivary flow rate increased in SS mice with DPSC-CM compared with that in the other groups. In addition, the number of inflammation sites in SMGs of the mice administered with DPSC-CM was lower than that in the other groups. The expression levels of interleukin (Il)-10 and transforming growth factor-β1 were upregulated in the DPSC-CM group, whereas those of Il-4 and Il-17a were downregulated. The DPSC-CM-administered group presented with a significantly increased percentage of regulatory T (Treg) cells and a significantly decreased percentage of type 17 Th (Th17) cells compared with the other groups. Conclusions These results indicated that DPSC-CM ameliorated SS by promoting Treg cell differentiation and inhibiting Th17 cell differentiation in the mouse spleen.

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The instability derived from the cochlear model is a phenomenon used to characterize its active processing, which is one of the fundamentals of hearing. This processing relates to the activities of outer hair cells (OHCs) lining in the cochlea. The decline of this processing function is accounted for by the spatially irregular activities of OHCs. Current cochlear models show excessive instability when cochlea containing the irregular activity of the OHCs is simulated. To explain this phenomenon, there are two possibilities. First, excessive instability may be essential to the model. Second, discretized errors may affect the instability of the model in numerical calculation. To investigate these possibilities, a state space model of two-dimensional cochlear mechanics is developed and applied to a high-accuracy scheme of numerical calculation. As a result of this simulation, the basilar membrane responses include the discretization error, which depends on the modeling accuracy. Furthermore, the transfer function and the temporal response show more instability with higher modeling accuracy, with the irregularity of the feedback gain corresponding to the activities of the OHCs. Therefore, when the discretization error is large, the instability is weakened. Consequently, this paper concludes that excessive instability is an essential feature of the cochlear model.