Human dental pulp harbours unique stem cell population exhibiting mesenchymal stem/stromal cell (MSC) characteristics. This study aimed to analyse the differentiation potential and other essential functional and morphological features of dental pulp stem cells (DPSCs) in comparison with Wharton’s jelly-derived MSCs from the umbilical cord (UC-MSCs), and to evaluate the osteogenic differentiation of DPSCs in 3D culture with a hypoxic microenvironment resembling the stem cell niche. Human DPSCs as well as UC-MSCs were isolated from primary human tissues and were subjected to a series of experiments. We established a multiantigenic profile of DPSCs with CD45⁻/CD14⁻/CD34⁻/CD29⁺/CD44⁺/CD73⁺/CD90⁺/CD105⁺/Stro-1⁺/HLA-DR⁻ (using flow cytometry) and confirmed their tri-lineage osteogenic, chondrogenic, and adipogenic differentiation potential (using qRT-PCR and histochemical staining) in comparison with the UC-MSCs. The results also demonstrated the potency of DPSCs to differentiate into osteoblasts in vitro. Moreover, we showed that the DPSCs exhibit limited cardiomyogenic and endothelial differentiation potential. Decreased proliferation and metabolic activity as well as increased osteogenic differentiation of DPSCs in vitro, attributed to 3D cell encapsulation and low oxygen concentration, were also observed. DPSCs exhibiting elevated osteogenic potential may serve as potential candidates for a cell-based product for advanced therapy, particularly for bone repair. Novel tissue engineering approaches combining DPSCs, 3D biomaterial scaffolds, and other stimulating chemical factors may represent innovative strategies for pro-regenerative therapies.

: Chronic inflammatory processes within the central nervous system (CNS) are in part responsible for the development of neurodegenerative and psychiatric diseases. These processes are associated with, among other things, the increased and disturbed activation of microglia and the elevated production of proinflammatory factors. Recent studies indicated that the disruption of the process of resolution of inflammation (RoI) may be the cause of CNS disorders. It is shown that the RoI is regulated by endogenous molecules called specialized pro-resolving mediators (SPMs), which interact with specific membrane receptors. Some SPMs activate formyl peptide receptors (FPRs), which belong to the family of seven-transmembrane G protein-coupled receptors. These receptors take part not only in the proinflammatory response but also in the resolution of the inflammation process. Therefore, the activation of FPRs might have complex consequences.: This review discusses the potential role of FPRs, and in particular the role of FPR2 subtype, in the brain under physiological and pathological conditions and their involvement in processes underlying neurodegenerative and psychiatric disorders as well as ischemia, the pathogenesis of which involves the dysfunction of inflammatory processes.

Prolonged or excessive microglial activation may lead to disturbances in the resolution of inflammation (RoI). The importance of specialized pro-resolving lipid mediators (SPMs) in RoI has been highlighted. Among them, lipoxins (LXA4) and aspirin-triggered lipoxin A4 (AT-LXA4) mediate beneficial responses through the activation of N-formyl peptide receptor-2 (FPR2). We aimed to shed more light on the time-dependent protective and anti-inflammatory impact of the endogenous SPMs, LXA4, and AT-LXA4, and of a new synthetic FPR2 agonist MR-39, in lipopolysaccharide (LPS)-exposed rat microglial cells. Our results showed that LXA4, AT-LXA4, and MR-39 exhibit a protective and pro-resolving potential in LPS-stimulated microglia, even if marked differences were apparent regarding the time dependency and efficacy of inhibiting particular biomarkers. The LXA4 action was found mainly after 3 h of LPS stimulation, and the AT-LXA4 effect was varied in time, while MR-39′s effect was mainly observed after 24 h of stimulation by endotoxin. MR-39 was the only FPR2 ligand that attenuated LPS-evoked changes in the mitochondrial membrane potential and diminished the ROS and NO release. Moreover, the LPS-induced alterations in the microglial phenotype were modulated by LXA4, AT-LXA4, and MR-39. The anti-inflammatory effect of MR-39 on the IL-1β release was mediated through FPR2. All tested ligands inhibited TNF-α production, while AT-LXA4 and MR-39 also diminished IL-6 levels in LPS-stimulated microglia. The favorable action of LXA4 and MR-39 was mediated through the inhibition of ERK1/2 phosphorylation. AT-LXA4 and MR39 diminished the phosphorylation of the transcription factor NF-κB, while AT-LXA4 also affected p38 kinase phosphorylation. Our results suggest that new pro-resolving synthetic mediators can represent an attractive treatment option for the enhancement of RoI, and that FPR2 can provide a perspective as a target in immune-related brain disorders.

Cell stiffening induced by anticancer microtubule targeting drugs (MTDs) such as vinflunine (VFL), colchicine (COL), and docetaxel (DTX) can be driven by crosstalk between actin filaments and microtubules.

Evidence indicates that adverse experiences in early life may be a factor for immune disturbances leading to the depression in adulthood. Recently, a pivotal role in the pathogenesis of depression has been assigned to the activation of the brain Nod-like receptor pyrin-containing 3 (NLRP3) inflammasome. We investigated the impact of chronic treatment with antidepressant drugs on the behavioral disturbances and the levels of proinflammatory factors in the hippocampus and frontal cortex of adult male rats after prenatal stress exposure. Next, we explored the involvement of the NLRP3 inflammasome-related pathways in the mechanism of antidepressant action. Our study confirmed that chronic antidepressant treatment attenuated depression-like disturbances and exerted an anxiolytic action. All antidepressants diminished the prenatal stress-induced increase in IL-1β in both brain areas, while IL-18 only in the hippocampus. Moreover, tianeptine administration diminished the increase in CCR2 levels in both brain areas, while in the hippocampus, tianeptine, along with venlafaxine CCL2 and iNOS levels. Next, we observed that in the hippocampus, tianeptine and fluoxetine suppressed upregulation of TLR4. Furthermore, venlafaxine suppressed NFкB p65-subunit phosphorylation, while fluoxetine enhanced the IкB level. Importantly, in the hippocampus, all antidepressants normalized evoked by stress changes in caspase-1 level, while tianeptine and venlafaxine also affect the levels of ASC and NLRP3 subunits. Our results provide new evidence that chronic administration of antidepressants exerts anti-inflammatory effects more pronounced in the hippocampus, through suppression of the NLRP3 inflammasome activation. These effects are accompanied by an improvement in the behavioral dysfunctions evoked by prenatal stress.

The dental pulp is the inner part of the tooth responsible for properly functioning during its lifespan. Apart from the very big biological heterogeneity of dental cells, tooth microenvironments differ a lot in the context of mechanical properties—ranging from 5.5 kPa for dental pulp to around 100 GPa for dentin and enamel. This physical heterogeneity and complexity plays a key role in tooth physiology and in turn, is a great target for a variety of therapeutic approaches. First of all, physical mechanisms are crucial for the pain propagation process from the tooth surface to the nerves inside the dental pulp. On the other hand, the modulation of the physical environment affects the functioning of dental pulp cells and thus is important for regenerative medicine. In the present review, we describe the physiological significance of biomechanical processes in the physiology and pathology of dental pulp. Moreover, we couple those phenomena with recent advances in the fields of bioengineering and pharmacology aiming to control the functioning of dental pulp cells, reduce pain, and enhance the differentiation of dental cells into desired lineages. The reviewed literature shows great progress in the topic of bioengineering of dental pulp—although mainly in vitro. Apart from a few positions, it leaves a gap for necessary filling with studies providing the mechanisms of the mechanical control of dental pulp functioning in vivo.