A macrophage shift from the M1 to the M2 phenotype is relevant for promoting tissue repair and regeneration. In a previous in vivo study, we found that direct current (DC) electrical stimulation (EStim) increased the proportion of M2 macrophages in healing tissues and directed the balance of the injury response away from healing/scarring towards regeneration. These observations led us to hypothesize that DC EStim regulates macrophage polarization towards an M2 phenotype. THP-1-derived M0, M1 (IFN-γ and LPS), and M2 (IL-4 and IL-13) macrophages were exposed (or not: control group) to 100 mV/mm of DC EStim, 1 h/day for three days. Macrophage polarization was assessed through gene and surface marker expressions and cytokine secretion profiles. Following DC EStim treatment, M0 cells exhibited an upregulation of M2 marker genes IL10, CD163, and PPARG. In M1 cells, DC EStim upregulated the gene expressions of M2 markers IL10, TGM2, and CD206 and downregulated M1 marker gene CD86. EStim treatment also reduced the surface expression of CD86 and secretion of pro-inflammatory cytokines IL-1β and IL-6. Our results suggest that DC EStim differentially exerts pro-M2 effects depending on the macrophage phenotype: it upregulates typical M2 genes in M0 and M1 cells while inhibiting M1 marker CD86 at the nuclear and protein levels and the secretion of pro-inflammatory interleukins in M1 cells. Conversely, M2 cells appear to be less responsive to the EStim treatment employed in this study.

Omega-3 polyunsaturated fatty acids (ω-3 PUFAs) are relevant to fetal and infant growth and development. Objective: to assess whether long-term exposure to dietary ω-3 PUFA imbalance alters pre- and/or postnatal pups' development and reproductive function later in life. Mice dams were fed with ω-3 PUFA Control (soybean oil, 7%), Deficient (sunflower oil, 7%) or Excess (blend oil; 4.2% cod-liver+2.8% soybean) diet before conception and throughout gestation-lactation and later on, their pups received the same diet from weaning to adulthood. Offspring somatic, neurobiological and reproductive parameters were evaluated. Excess pups were lighter during the preweaning period and shorter in length from postnatal day (PND) 7 to 49, compared to Control pups (P<.05). On PND14, the percentage of pups with eye opening in Excess group was lower than those from Control and Deficient groups (P<.05). In Excess female offspring, puberty onset (vaginal opening and first estrus) occurred significantly later and the percentage of parthenogenetic oocytes on PND63 was higher than Control and Deficient ones (P<.05). Deficient pups were shorter in length (males: on PND14, 21, 35 and 49; females: on PND14, 21 and 42) compared with Control pups (P<.05). Deficient offspring exhibited higher percentage of bending spermatozoa compared to Control and Excess offspring (P<.05). These results show that either an excessively high or insufficient ω-3 PUFA consumption prior to conception until adulthood seems inadvisable because of the potential risks of short-term adverse effects on growth and development of the progeny or long-lasting effects on their reproductive maturation and function.

Electrical stimulation (EStim), whether used alone or in combination with bone tissue engineering (BTE) approaches, has been shown to promote bone healing. In our previous in vitro studies, mesenchymal stem cells (MSCs) were exposed to EStim and a sustained, long-lasting increase in osteogenic activity was observed. Based on these findings, we hypothesized that pretreating MSC with EStim, in 2D or 3D cultures, before using them to treat large bone defects would improve BTE treatments. Critical size femur defects were created in 120 Sprague–Dawley rats and treated with scaffold granules seeded with MSCs that were pre-exposed or not (control group) to EStim 1 h/day for 7 days in 2D (MSCs alone) or 3D culture (MSCs + scaffolds). Bone healing was assessed at 1, 4, and 8 weeks post-surgery. In all groups, the percentage of new bone increased, while fibrous tissue and CD68+ cell count decreased over time. However, these and other healing features, like mineral density, bending stiffness, the amount of new bone and cartilage, and the gene expression of osteogenic markers, did not significantly differ between groups. Based on these findings, it appears that the bone healing environment could counteract the long-term, pro-osteogenic effects of EStim seen in our in vitro studies. Thus, EStim seems to be more effective when administered directly and continuously at the defect site during bone healing, as indicated by our previous studies.

Since their initial recognition, miRNAs have been the subject of rising scientific interest. Especially in recent years, miRNAs have been recognized to play an important role in the mediation of various diseases, and further, their potential as biomarkers was recognized. Rising attention has also been given to miRNA-21, which has proven to play an ambivalent role as a biomarker. Responding to the demand for biomarkers in the trauma field, the present review summarizes the contrary roles of miRNA-21 in acute organ damage after trauma with a specific focus on the role of miRNA-21 in traumatic brain injury, spinal cord injury, cardiac damage, lung injury, and bone injury. This review is based on a PubMed literature search including the terms “miRNA-21” and “trauma”, “miRNA-21” and “severe injury”, and “miRNA-21” and “acute lung respiratory distress syndrome”. The present summary makes it clear that miRNA-21 has both beneficial and detrimental effects in various acute organ injuries, which precludes its utility as a biomarker but makes it intriguing for mechanistic investigations in the trauma field.