22The aetiology of many gestational disorders is still unknown. However, insufficient trans-

Preeclampsia is a devastating pregnancy disorder. Severity varies widely, and while severe preeclampsia often requires pre-term delivery, women with mild preeclampsia may reach term with minor interventions. The mechanisms that mediate disease severity are poorly understood, but may include adaptive processes by the placenta. We aimed to establish whether in pregnancies that reached term and those that delivered pre-term, the placental response to preeclampsia was intrinsically different, and explore potential adaptive mechanisms. Hydrogen peroxide production and antioxidant activity were increased in term preeclamptic placentae, whereas pre-term preeclamptic placentae had reduced hydrogen peroxide production and reduced function of the antioxidant system superoxide dismutase compared to control placentae. Markers of mitochondrial fission/fusion, apoptosis and the expression level of mitochondrial complexes were differentially disrupted in term compared to pre-term preeclamptic placentae. Mitochondrial respiration and content were increased in term preeclamptic placentae, but mitochondria had a lower respiratory reserve capacity. Mitochondrial respiration and hydrogen peroxide production were increased in healthy term placentae after in vitro hypoxia/reoxygenation. Placentae from preeclamptic pregnancies that reached term showed multiple adaptions that were not present in pre-term preeclamptic placentae. Increased antioxidant activity, and expression of markers of mitochondrial fusion and apoptotic suppression, may relate to salvaging damaged mitochondria. Increased mitochondrial respiration may allow ongoing tissue function even with reduced respiratory efficiency in term preeclamptic pregnancies. Response after in vitro hypoxia/reoxygenation suggests that disruption of oxygen supply is key to placental mitochondrial adaptations. Reactive oxygen species signalling in term preeclamptic placentae may be at a level to trigger compensatory antioxidant and mitochondrial responses, allowing tissue level maintenance of function when there is organelle level dysfunction.

Chronic wounds present a significant burden to the health care system and the patient. Ozone therapy has been proposed as a treatment for chronic wounds, potentially acting by eliciting mild oxidative stress or disinfection. The purpose of this systematic review is to evaluate the potential benefits and harms of ozone therapy as an advanced care intervention for chronic wounds. Studies were extracted from Google Scholar, PubMed, the Cochrane Library, and reference lists. General inclusion criteria included English-language randomised human trials reporting the use of ozone therapy in the topical treatment of chronic wounds. Primary outcome data included the extent of chronic wound healing, and secondary outcomes included adverse effects. Studies were assessed for level of bias and data quality. Nine studies (n = 453 patients) matched the inclusion criteria and underwent meta-analysis. Overall, there was a significant improvement in wound closure with ozone therapy. Results consistently favour the application of ozone as a treatment for chronic wounds; however, there is no conclusive evidence of ozone therapy as superior compared with standard treatments. Compared with standard care, ozone therapy as an advanced wound care treatment may improve the proportion of chronic wounds healed in a shorter amount of time, but further research is required.

Key points Inappropriate intake of key micronutrients in pregnancy is known to alter maternal endocrine status, impair placental development and induce fetal growth restriction. Selenium is an essential micronutrient required for the function of approximately 25 important proteins. However, the specific effects of selenium deficiency during pregnancy on maternal, placental and fetal outcomes are poorly understood. The present study demonstrates that maternal selenium deficiency increases maternal triiodothyronine and tetraiodothyronine concentrations, reduces fetal blood glucose concentrations, and induces fetal growth restriction. Placental expression of key selenium‐dependent thyroid hormone converting enzymes were reduced, whereas the expression of key placental nutrient transporters was dysregulated. Selenium deficiency had minimal impact on selenium‐dependent anti‐oxidants but increased placental copper concentrations and expression of superoxide dismutase 1. These results highlight the idea that selenium deficiency during pregnancy may contribute to thyroid dysfunction, causing reduced fetal growth, that may precede programmed disease outcomes in offspring. Abstract Selenium is a trace element fundamental to diverse homeostatic processes, including anti‐oxidant regulation and thyroid hormone metabolism. Selenium deficiency in pregnancy is common and increases the risk of pregnancy complications including fetal growth restriction. Although altered placental formation may contribute to these poor outcomes, the mechanism by which selenium deficiency contributes to complications in pregnancy is poorly understood. Female C57BL/6 mice were randomly allocated to control (>190 µg kg–1, n = 8) or low selenium (<50 µg kg–1, n = 8) diets 4 weeks prior to mating and throughout gestation. Pregnant mice were killed at embryonic day 18.5 followed by collection of maternal and fetal tissue. Maternal and fetal plasma thyroid hormone concentrations were analysed, as was placental expression of key selenoproteins involved in thyroid metabolism and anti‐oxidant defences. Selenium deficiency increased plasma tetraiodothyronine and triiodothyronine concentrations. This was associated with a reduction in placental expression of key selenodependent deiodinases, DIO2 and DIO3. Placental expression of selenium‐dependent anti‐oxidants was unaffected by selenium deficiency. Selenium deficiency reduced fetal glucose concentrations, leading to reduced fetal weight. Placental glycogen content was increased within the placenta, as was Slc2a3 mRNA expression. This is the first study to demonstrate that selenium deficiency may reduce fetal weight through increased maternal thyroid hormone concentrations, impaired placental thyroid hormone metabolism and dysregulated placental nutrient transporter expression. The study suggests that the magnitude of selenium deficiency commonly reported in pregnant women may be sufficient to impair thyroid metabolism but not placental anti‐oxidant concentrations.

Pregnancy is one of the greatest physiological challenges that a women can experience. The physiological adaptations that accompany pregnancy may increase the risk of developing a number of disorders that can lead to both acute and chronic physiological outcomes. In addition, fetal development may be impaired and, if the fetus survives, the child may be at an increased risk of disease throughout life. Pregnancy disorders are poorly predicted by traditional risk factors and maternal history alone. The identification of biomarkers that can predict incidence and severity of disease would allow for improved and targeted prophylactic therapies to prevent adverse maternal and fetal outcomes. Many of these pregnancy disorders, including preeclampsia, intrauterine growth restriction, gestational diabetes mellitus and preterm birth are known to be regulated at least in part by poor trophoblast invasion and/or dysregulated placental function. Cellular stress within the placenta increases the release of a number of factors into the maternal circulation. While many of these factors minimally impact maternal biology, others affect key physiological systems and contribute to disease. Importantly, these factors may be detected in physiological fluids and have predictive capacity making them ideal candidates as biomarkers of pregnancy disorders. This review will discuss what is known about these placental derived biomarkers of pregnancy disorders and highlight potential clinical opportunities for disease prediction and diagnosis.

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Mitochondria are essential cellular organelles, controlling multiple signalling pathways critical for cell survival and cell death. Increasing evidence suggests that mitochondrial metabolism and functions are indispensable in tumorigenesis and cancer progression, rendering mitochondria and mitochondrial functions as plausible targets for anti-cancer therapeutics. In this review, we summarised the major strategies of selective targeting of mitochondria and their functions to combat cancer, including targeting mitochondrial metabolism, the electron transport chain and tricarboxylic acid cycle, mitochondrial redox signalling pathways, and ROS homeostasis. We highlight that delivering anti-cancer drugs into mitochondria exhibits enormous potential for future cancer therapeutic strategies, with a great advantage of potentially overcoming drug resistance. Mitocans, exemplified by mitochondrially targeted vitamin E succinate and tamoxifen (MitoTam), selectively target cancer cell mitochondria and efficiently kill multiple types of cancer cells by disrupting mitochondrial function, with MitoTam currently undergoing a clinical trial.

Epilepsy is a neurological disorder that affects approximately 50 million people worldwide. There is currently no definitive epilepsy cure. However, in recent years, medicinal cannabis has been successfully trialed as an effective treatment for managing epileptic symptoms, but whose mechanisms of action are largely unknown. Lately, there has been a focus on neuroinflammation as an important factor in the pathology of many epileptic disorders. In this literature review, we consider the links that have been identified between epilepsy, neuroinflammation, the endocannabinoid system (ECS), and how cannabinoids may be potent alternatives to more conventional pharmacological therapies. We review the research that demonstrates how the ECS can contribute to neuroinflammation, and could therefore be modulated by cannabinoids to potentially reduce the incidence and severity of seizures. In particular, the cannabinoid cannabidiol has been reported to have anti-convulsant and anti-inflammatory properties, and it shows promise for epilepsy treatment. There are a multitude of signaling pathways that involve endocannabinoids, eicosanoids, and associated receptors by which cannabinoids could potentially exert their therapeutic effects. Further research is needed to better characterize these pathways, and consequently improve the application and regulation of medicinal cannabis.