The ketogenic diet (KD) has been used as a treatment for epilepsy since the 1920s, and its role in the prevention of many other diseases is now being considered. In recent years, there has been an intensive investigation on using the KD as a therapeutic approach to treat acute pathologies, including ischemic ones. However, contradictory data are observed for the effects of the KD on various organs after ischemic injury. In this review, we provide the first systematic analysis of studies conducted from 1980 to 2022 investigating the effects and main mechanisms of the KD and its mimetics on ischemia–reperfusion injury of the brain, heart, kidneys, liver, gut, and eyes. Our analysis demonstrated a high diversity of both the composition of the used KD and the protocols for the treatment of animals, which could be the reason for contradictory effects in different studies. It can be concluded that a true KD or its mimetics, such as β-hydroxybutyrate, can be considered as positive exposure, protecting the organ from ischemia and its negative consequences, whereas the shift to a rather similar high-calorie or high-fat diet leads to the opposite effect.

The positive effects of female sex hormones, particularly estradiol and progesterone, have been observed in treatment of various pathologies. Acute kidney injury (AKI) is a common condition in hospitalized patients in which the molecular mechanisms of hormone action are poorly characterized. In this study, we investigated the influence of estradiol and progesterone on renal cells during ischemic injury. We performed both in vivo experiments on female and male rats and in vitro experiments on renal tubular cells (RTCs) obtained from the kidneys of intact animals of different sexes. Since mitochondria play an important role in the pathogenesis of AKI, we analyzed the properties of individual mitochondria in renal cells, including the area, roundness, mitochondrial membrane potential, and mitochondrial permeability transition pore (mPTP) opening time. We found that pre-treatment with progesterone or estradiol attenuated the severity of ischemia/reperfusion (I/R)-induced AKI in female rats, whereas in male rats, these hormones exacerbated renal dysfunction. We demonstrated that the mPTP opening time was higher in RTCs from female rats than that in those from male rats, which may be one of the reasons for the higher tolerance of females to ischemic injury. In RTCs from the kidneys of male rats, progesterone caused mitochondrial fragmentation, which can be associated with reduced cell viability. Thus, therapy with progesterone or estradiol displays quite different effects depending on sex, and could be only effective against ischemic AKI in females.

Introduction: The study aimed to investigate the effects of low concentrations of mitochondrial uncouplers in endothelial cells on the CpG dinucleotide methylation of the ICAM1 gene promoter. The excessive inflammatory response in the endothelium is responsible for the development of many cardiovascular diseases. Mitochondria are important regulators of endothelial cell functions. Mild uncoupling of oxidative phosphorylation and respiration in endothelial mitochondria exerts a long lasting anti-inflammatory effect. However, the detailed mechanism of the anti-inflammatory activity of mitochondrial uncouplers remains unclear.We hypothesized that mild mitochondrial uncoupling leads to epigenetic changes in genomic DNA contributing to the anti-inflammatory response. Methods: We studied the long-term effects of mitochondria-targeted compounds with the uncoupler’s activities: the antioxidant plastoquinonyl-decyl-triphenylphosphonium (SkQ1), dodecyl-triphenylphosphonium (C12TPP), and 2,4-dinitrophenol (DNP). The mRNA expression of the intercellular adhesion molecule 1 (ICAM1), a marker of inflammatory activation of endothelial cells, was measured by RT-qPCR. Cytosine methylation in the CpG sites of the ICAM1 gene promoter was estimated by bisulfite sequencing of individual clones. Results: It was found that downregulation of ICAM1 expression caused by DNP and C12TPP was accompanied by an increase in the methylation of CpG sites in the ICAM1 gene promoter. None of the compounds affected intracellular or intramitochondrial ATP levels. Conclusion: Low concentrations of mitochondrial oxidative phosphorylation uncouplers are able to increase methylation of ICAM1 gene promoter, which corresponds to the observed decrease in the levels of mRNA levels of this gene. Thus, the change in methylation of the ICAM1 gene promoter may underlie the mechanism of decreased ICAM1 expression caused by mild mitochondrial depolarization. Mitochondrial uncouplers may be exploited as possible therapeutic candidates to treat excessive inflammation in endothelium, by changing the methylation status of genomic DNA.

This study investigated the toxicity of ten polymer materials intended for the development of invasive neural interfaces improving the treatment of neurological diseases. Most of the materials for neural implants can cause traumatization of the surrounding tissue, inflammation, and foreign body reaction. In this study, in vitro and in vivo toxicity assessment was performed for nylon 618 (NY), polycaprolactone (PCL), polyethylene glycol diacrylate (PEGDA), polydimethylsiloxane (PDMS), polyethylene terephthalate (PET), polylactide (PLA), thermoplastic polyurethane (TPU), polypropylene (PP), polyethylene terephthalate glycol (PET-G), and polyimide (PI). The biocompatibility of these ten materials was assessed based on cell adhesion, growth and cytotoxicity on neural (PC-12) and fibroblast (NRK-49F) cultures. Furthermore, brain tissue responses to the implanted phantom scaffolds were analyzed in rats. According to these measurements, PI showed the highest compatibility for both cell types. PEGDA exhibited cytotoxic effects, low cell adhesion and the strongest foreign body reaction, including fibrosis and multinucleated cell formation. The other polymers showed lower pathological responses which makes them potentially usable for neural interfacing. We conclude that PEGDA appears to be unsuitable for long-term use due to adverse tissue and cellular reactions, whereas PI, PLA, PDMS and TPU hold promise as materials for safe and effective neural interface applications.

In this study, in a culture of renal epithelial cells, we identified those expressing nestin, a cytoskeletal protein associated with stem/progenitor/activated/proliferating cell states. A mouse expressing GFP under the nestin promoter was used, followed by cell isolation and culture. It is hypothesized that this can be used to assess the stem/progenitor/activated/proliferating cell level in a mixed kidney cell culture. Both nestin-positive and nestin-negative cells were demonstrated to be present in the culture. After visualization, cells were attached to a glass slide with a grid, fixed, and prepared for electron microscopy analysis, with each cell visually identified by light microscopy being analyzed. Electron microscopy revealed tight interactions between nestin-positive and nestin-negative cells. Significant differences in the ultrastructure of nestin-positive and nestin-negative cells were observed. Nestin-positive cells were distinguished by a high ribosome content, indicating high protein-synthesizing activity. In the nestin–GFP-high (sorted) population examined by electron microscopy, vesicle-containing protrusions were frequently observed. These cells could contain multiple nuclei of varying sizes and had a high content of lysosomes. No significant differences in mitochondrial ultrastructure were observed in nestin-positive and -negative cells, although functional characteristics evaluated by the membrane potential probe differed.