MitoQ protects against carbon tetrachloride-induced hepatocyte ferroptosis and acute liver injury by suppressing mtROS-mediated ACSL4 upregulation.

Ferroptosis has been shown to be involved in carbon tetrachloride (CCl4)-induced acute liver injury (ALI). The mitochondrion-targeted antioxidant MitoQ can eliminate the production of mitochondrial reactive oxygen species (mtROS). This study investigated the role of MitoQ in CCl4-induced hepatocytic ferroptosis and ALI. MDA and 4HNE were elevated in CCl4-induced mice. In vitro, CCl4 exposure elevated the levels of oxidized lipids in HepG2 cells. Alterations in the mitochondrial ultrastructure of hepatocytes were observed in the livers of CCl4-evoked mice. Ferrostatin-1 (Fer-1) attenuated CCl4-induced hepatic lipid peroxidation, mitochondrial ultrastructure alterations and ALI. Mechanistically, acyl-CoA synthetase long-chain family member 4 (ACSL4) was upregulated in CCl4-exposed human hepatocytes and mouse livers. The ACSL4 inhibitor rosiglitazone alleviated CCl4-induced hepatic lipid peroxidation and ALI. ACSL4 knockdown inhibited oxidized lipids in CCl4-exposed human hepatocytes. Moreover, CCl4 exposure decreased the mitochondrial membrane potential and OXPHOS subunit levels and increased the mtROS level in HepG2 cells. Correspondingly, MitoQ pretreatment inhibited the upregulation of ACSL4 in CCl4-evoked mouse livers and HepG2 cells. MitoQ attenuated lipid peroxidation in vivo and in vitro after CCl4 exposure. Finally, MitoQ pretreatment alleviated CCl4-induced hepatocytic ferroptosis and ALI. These findings suggest that MitoQ protects against hepatocyte ferroptosis in CCl4-induced ALI via the mtROS-ACSL4 pathway.

MitoQ relieves mitochondrial dysfunction in UVA and cigarette smoke-induced Fuchs endothelial corneal dystrophy.

Fuchs endothelial corneal dystrophy (FECD), a degenerative corneal condition, is characterized by the droplet-like accumulation of the extracellular matrix, known as guttae and progressive loss of corneal endothelial cells ultimately leading to visual distortion and glare. FECD can be influenced by environmental stressors and genetic conditions. However, the role of mitochondrial dysfunction for advancing FECD pathogenesis is not yet fully studied. Therefore, in the present study we sought to determine whether a combination of environmental stressors (ultraviolet-A (UVA) light and cigarette smoke condensate (CSC)) can induce mitochondrial dysfunction leading to FECD. We also investigated if MitoQ, a water-soluble antioxidant, can target mitochondrial dysfunction induced by UVA and CSC in human corneal endothelial cells mitigating FECD pathogenesis. We modeled the FECD by increasing exogenous oxidative stress with CSC (0.2%), UVA (25J/cm2) and a combination of UVA+CSC and performed a temporal analysis of their cellular and mitochondrial effects on HCEnC-21T immortalized cells in vitro before and after MitoQ (0.05 µM) treatment. Interestingly, we observed that a combination of UVA+CSC exposure increased mitochondrial ROS and fragmentation leading to a lower mitochondrial membrane potential and increased levels of cytochrome c release leading to apoptosis and cell death. MitoQ intervention successfully mitigated these effects and restored cell viability. The UVA+CSC model could be used to study stress induced mitochondrial dysfunction. Additionally, MitoQ can serve as a viable antioxidant in attenuating mitochondrial dysfunction, underscoring its potential as a molecular-focused treatment approach to combat FECD pathogenesis.

Mitofilin in cardiovascular diseases: Insights into the pathogenesis and potential pharmacological interventions.

The impact of mitochondrial dysfunction on the pathogenesis of cardiovascular disease is increasing. However, the precise underlying mechanism remains unclear. Mitochondria produce cellular energy through oxidative phosphorylation while regulating calcium homeostasis, cellular respiration, and the production of biosynthetic chemicals. Nevertheless, problems related to cardiac energy metabolism, defective mitochondrial proteins, mitophagy, and structural changes in mitochondrial membranes can cause cardiovascular diseases via mitochondrial dysfunction. Mitofilin is a critical inner mitochondrial membrane protein that maintains cristae structure and facilitates protein transport while linking the inner mitochondrial membrane, outer mitochondrial membrane, and mitochondrial DNA transcription. Researchers believe that mitofilin may be a therapeutic target for treating cardiovascular diseases, particularly cardiac mitochondrial dysfunctions. In this review, we highlight current findings regarding the role of mitofilin in the pathogenesis of cardiovascular diseases and potential therapeutic compounds targeting mitofilin.

Risks of using mitoquinone during in vitro maturation and its potential protective effects against lipotoxicity-induced oocyte mitochondrial stress.

PURPOSE: Oxidative stress and mitochondrial dysfunction play central roles in reduced oocyte quality and infertility in obese patients. Mitochondria-targeted treatments containing co-enzyme Q10 such as mitoquinone (MitoQ) can increase mitochondrial antioxidative capacity; however, their safety and efficiency when supplemented to oocytes under lipotoxic conditions have not been described. METHODS: We tested the effect of different concentrations of MitoQ or its cationic carrier (TPP) (0, 0.1, 0.5, 1.0 µM each) during bovine oocyte IVM. Then, we tested the protective capacity of MitoQ (0.1 µM) against palmitic acid (PA)-induced lipotoxicity and mitochondrial dysfunction in oocytes. RESULTS: Exposure to MitoQ, or TPP only, at 1 µM significantly (P<0.05) reduced oocyte mitochondrial inner membrane potential (JC-1 staining) and resulted in reduced cleavage and blastocyst rates compared with solvent control. Lower concentrations of MitoQ or TPP had no effects on embryo development under control (PA-free) conditions. As expected, PA increased the levels of MMP and ROS in oocytes (CellROX staining) and reduced cleavage and blastocyst rates compared with the controls (P<0.05). These negative effects were ameliorated by 0.1 µM MitoQ. In contrast, 0.1 µM TPP alone had no protective effects. MitoQ also normalized the expression of HSP10 and TFAM, and partially normalized HSP60 in the produced blastocysts, indicating at least a partial alleviation of PA-induced mitochondrial stress. CONCLUSION: Oocyte exposure to MitoQ may disturb mitochondrial bioenergetic functions and developmental capacity due to a TPP-induced cationic overload. A fine-tuned concentration of MitoQ can protect against lipotoxicity-induced mitochondrial stress during IVM and restore developmental competence and embryo quality.

SkQ3 Exhibits the Most Pronounced Antioxidant Effect on Isolated Rat Liver Mitochondria and Yeast Cells.

Oxidative stress is involved in a wide range of age-related diseases. A critical role has been proposed for mitochondrial oxidative stress in initiating or promoting these pathologies and the potential for mitochondria-targeted antioxidants to fight them, making their search and testing a very urgent task. In this study, the mitochondria-targeted antioxidants SkQ1, SkQ3 and MitoQ were examined as they affected isolated rat liver mitochondria and yeast cells, comparing SkQ3 with clinically tested SkQ1 and MitoQ. At low concentrations, all three substances stimulated the oxidation of respiratory substrates in state 4 respiration (no ADP addition); at higher concentrations, they inhibited the ADP-triggered state 3 respiration and the uncoupled state, depolarized the inner mitochondrial membrane, contributed to the opening of the mPTP (mitochondrial permeability transition pore), did not specifically affect ATP synthase, and had a pronounced antioxidant effect. SkQ3 was the most active antioxidant, not possessing, unlike SkQ1 or MitoQ, prooxidant activity with increasing concentrations. In yeast cells, all three substances reduced prooxidant-induced intracellular oxidative stress and cell death and prevented and reversed mitochondrial fragmentation, with SkQ3 being the most efficient. These data allow us to consider SkQ3 as a promising potential therapeutic agent to mitigate pathologies associated with oxidative stress.

Mitoquinone Mesylate and Mitochondrial DNA in End Organs in Humanized Mouse Model of Chronic Treated Human Immunodeficiency Virus Infection.

No treatment exists for mitochondrial dysfunction, a contributor to end-organ disease in human immunodeficiency virus (HIV). The mitochondrial antioxidant mitoquinone mesylate (MitoQ) attenuates mitochondrial dysfunction in preclinical mouse models of various diseases but has not been used in HIV. We used a humanized murine model of chronic HIV infection and polymerase chain reaction to show that HIV-1-infected mice treated with antiretroviral therapy and MitoQ for 90 days had higher ratios of human and murine mitochondrial to nuclear DNA in end organs compared with HIV-1-infected mice on antiretroviral therapy. We offer translational evidence of MitoQ as treatment for mitochondrial dysfunction in HIV.

Mitoquinone mesylate attenuates pathological features of lean and obese allergic asthma in mice.

Obesity is associated with severe, difficult-to-control asthma, and increased airway oxidative stress. Mitochondrial reactive oxygen species (mROS) are an important source of oxidative stress in asthma, leading us to hypothesize that targeting mROS in obese allergic asthma might be an effective treatment. Using a mouse model of house dust mite (HDM)-induced allergic airway disease in mice fed a low- (LFD) or high-fat diet (HFD), and the mitochondrial antioxidant MitoQuinone (MitoQ), we investigated the effects of obesity and ROS on HDM-induced airway inflammation, remodeling, and airway hyperresponsiveness (AHR). Obese allergic mice showed increased lung tissue eotaxin, airway tissue eosinophilia, and AHR compared with lean allergic mice. MitoQ reduced airway inflammation, remodeling, and hyperreactivity in both lean and obese allergic mice, and tissue eosinophilia in obese-allergic mice. Similar effects were observed with decyl triphosphonium (dTPP+), the hydrophobic cationic moiety of MitoQ lacking ubiquinone. HDM-induced oxidative sulfenylation of proteins was increased particularly in HFD mice. Although only MitoQ reduced sulfenylation of proteins involved in protein folding in the endoplasmic reticulum (ER), ER stress was attenuated by both MitoQ and dTPP+ suggesting the anti-allergic effects of MitoQ are mediated in part by effects of its hydrophobic dTPP+ moiety reducing ER stress. In summary, oxidative signaling is an important mediator of allergic airway disease. MitoQ, likely through reducing protein oxidation and affecting the UPR pathway, might be effective for the treatment of asthma and specific features of obese asthma.

A mitochondrial-targeted antioxidant (MitoQ) improves motor coordination and reduces Purkinje cell death in a mouse model of ARSACS.

Mitochondrial deficits have been observed in animal models of Autosomal-recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) and in patient-derived fibroblasts. We investigated whether mitochondrial function could be restored in Sacs-/- mice, a mouse model of ARSACS, using the mitochondrial-targeted antioxidant ubiquinone MitoQ. After 10weeks of chronic MitoQ administration in drinking water, we partially reversed motor coordination deficits in Sacs-/- mice but did not affect litter-matched wild-type control mice. MitoQ administration led to a restoration of superoxide dismutase 2 (SOD2) in cerebellar Purkinje cell somata without altering Purkinje cell firing deficits. Purkinje cells in anterior vermis of Sacs-/- mice normally undergo cell death in ARSACS; however, Purkinje cells numbers were elevated after chronic MitoQ treatment. Furthermore, Purkinje cell innervation of target neurons in the cerebellar nuclei of Sacs-/- mice was also partially restored with MitoQ treatment. Our data suggest that MitoQ is a potential therapeutic treatment for ARSACS and that it improves motor coordination via increasing cerebellar Purkinje cell mitochondria function and reducing Purkinje cell death.

Protective effects of different doses of MitoQ separately and combined with trehalose on oxidative stress and sperm function of cryopreserved Markhoz goat semen.

The mitochondria-targeted antioxidant MitoQ has been regarded as an effective antioxidant agent against cryo-induced oxidative cellular damage. This study aimed to evaluate the use of different doses of MitoQ combined with trehalose to minimize mitochondrial impairment and oxidative stress during sperm cryopreservation of Markhoz goat. For this, semen samples (n = 50) were collected by electroejaculation every 5 days from 5 bucks in 10 replicates. On each collection day, 5 ejaculates (one ejaculate for each buck) were pooled and then diluted in eight different Tris-based extenders as follows: no additives (control), 20, 200, 2000 nM of MitoQ (MT20, MT200, MT 2000, respectively), 150 mM of trehalose (Tr), MT20+Tr, MT200+Tr, MT2000+Tr. The semen samples were frozen using a standard protocol, and sperm function and oxidative stress were evaluated after thawing. The semen extender supplemented with MT200+Tr had higher (P < 0.05) total and progressive motility, acrosome and membrane integrity, superoxide dismutase, glutathione peroxidase, total antioxidant capacity, and lower (P < 0.05) DNA fragmentation, malondialdehyde and intracellular hydrogen peroxide levels than the all other groups except MT200; meanwhile, MT200 was also improved (P < 0.05) in these parameters than in the control group. Furthermore, MT200 and MT200+Tr showed higher (P < 0.05) percentages of live cryopreserved sperm with high mitochondrial activity than other groups. However, abnormality percentage and catalase activity of frozen-thawed sperm were not affected by treatments (P > 0.05). To conclude, we have found that supplementation of 200 nM MitoQ alone or in combination with 150 mM trehalose to semen extender improved the quality of cryopreserved sperm in goats, which is associated with enhanced antioxidant enzymatic defense and mitochondrial activity and reduced DNA fragmentation.

MitoQ Protects Ovarian Organoids against Oxidative Stress during Oogenesis and Folliculogenesis In Vitro.

Ovarian organoids, based on mouse female germline stem cells (FGSCs), have great value in basic research and are a vast prospect in pre-clinical drug screening due to their properties, but the competency of these in vitro-generated oocytes was generally low, especially, in vitro maturation (IVM) rate. Recently, it has been demonstrated that the 3D microenvironment triggers mitochondrial dysfunction during follicle growth in vitro. Therefore, therapies that protect mitochondria and enhance their function in oocytes warrant investigation. Here, we reported that exposure to 100 nM MitoQ promoted follicle growth and maturation in vitro, accompanied by scavenging ROS, reduced oxidative injury, and restored mitochondrial membrane potential in oocytes. Mechanistically, using mice granulosa cells (GCs) as a cellular model, it was shown that MitoQ protects GCs against H2O2-induced apoptosis by inhibiting the oxidative stress pathway. Together, these results reveal that MitoQ reduces oxidative stress in ovarian follicles via its antioxidative action, thereby protecting oocytes and granulosa cells and providing an efficient way to improve the quality of in vitro-generated oocytes.

Mitoquinone Alleviates Donation after Cardiac Death Kidney Injury during Hypothermic Machine Perfusion in Rat Model.

Transplanted organs are subjected to harmful conditions through stopping blood flow, hypothermic storage of the graft, and subsequent reperfusion. In particular, kidneys donated from patients after cardiac arrest (DCD) are classified as more vulnerable to ischemia-reperfusion injury (IRI). Hypothermic machine perfusion is proposed as a solution for better kidney storage before transplantation, and it is a good platform for additional graft treatment. Antioxidants have gained interest in regenerative medicine due to their ability to scavenge reactive oxygen species (ROS), which play a key role in IRI. We evaluated the effect of Mitoquinone (MitoQ), a strong mitochondria-targeted antioxidant, administered directly to the perfusing buffer. Rat kidneys were isolated, randomly classified into one of the following groups, donation after brainstem death (DBD), DCD, and DCD with MitoQ, and perfused for 22 hours with a hypothermic machine perfusion system. Subsequently, we detected levels of kidney injury (KIM-1) and oxidative stress (ROS/RNS, cytochrome C oxidase, and mitochondrial integrity) markers. We compared the activation of the apoptosis pathway (caspase 3 and 9), the concentration of phosphorylated Akt (pAkt), and the pAkt/total Akt ratio. MitoQ reduces KIM-1 concentration, total ROS/RNS, and the level of caspases. We observed a decrease in pAkt and the pAkt/total Akt ratio after drug administration. The length of warm ischemia time negatively impacts the graft condition. However, MitoQ added to the perfusing system as an 'on pump' therapy mitigates injury to the kidney before transplantation by inhibiting apoptosis and reducing ROS/RNS levels. We propose MitoQ as a potential drug for DCD graft preconditioning.

Mitochondria as Therapeutic Targets in Heart Failure.

PURPOSE OF REVIEW: We review therapeutic approaches aimed at restoring function of the failing heart by targeting mitochondrial reactive oxygen species (ROS), ion handling, and substrate utilization for adenosine triphosphate (ATP) production. RECENT FINDINGS: Mitochondria-targeted therapies have been tested in animal models of and humans with heart failure (HF). Cardiac benefits of sodium/glucose cotransporter 2 inhibitors might be partly explained by their effects on ion handling and metabolism of cardiac myocytes. The large energy requirements of the heart are met by oxidative phosphorylation in mitochondria, which is tightly regulated by the turnover of ATP that fuels cardiac contraction and relaxation. In heart failure (HF), this mechano-energetic coupling is disrupted, leading to bioenergetic mismatch and production of ROS that drive the progression of cardiac dysfunction. Furthermore, HF is accompanied by changes in substrate uptake and oxidation that are considered detrimental for mitochondrial oxidative metabolism and negatively affect cardiac efficiency. Mitochondria lie at the crossroads of metabolic and energetic dysfunction in HF and represent ideal therapeutic targets.

The effect of mitochondria-targeted antioxidant MitoQ10 on redox signaling pathway components in PCOS mouse model.

PURPOSE: Considerable evidence suggests that mitochondrial dysfunction and oxidative stress contribute to the pathogenesis of Polycystic ovary syndrome (PCOS). We aimed to evaluate the effectiveness of mitochondria-targeted antioxidant, MitoQ10, on the redox signaling pathway's component in PCOS. METHOD: We assessed TXNIP, TRX, and ASK1 expression in granulosa cells (GCs) of the DHEA-induced PCOS mouse model. Female BALB/c mice in five groups of Control, DHEA, and DHEA + MitoQ10 in three doses of 250, 500, and 750 µmol/L MitoQ10 were treated for 21 days. RESULTS: Histological investigation showed a probable improvement in folliculogenesis; besides, ASK1 and TXNIP expression were significantly increased in GCs of the PCOS mouse F4Fmodel as compared to the control groups and decreased steadily in groups treated by MitoQ10. However, TRX expression showed a drop that was restored by MitoQ10 meaningfully (P ≤ 0.05). CONCLUSION: The work presented herein suggests mitochondria-targeted antioxidant, MitoQ10, have modulating effects on folliculogenesis in the ovary and also on the redox signaling pathway in GCs of PCOS mouse model which may have potential to attenuate oxidative stress and its relative damages.

Mitoquinone does not improve sperm cryo-resistance in bulls.

Oxidative stress is associated with impaired post-thaw sperm quality. As mitochondria are the main source of reactive oxygen species (ROS) in sperm, the goal of this study was to evaluate effects of the mitochondria-targeting antioxidant Mitoquinone (MitoQ) during cryopreservation of bull sperm. Semen was collected from 11 Simmental bulls (two ejaculates per bull) and diluted in Triladyl® supplemented with various concentrations of MitoQ (0, 0.2, 2, and 20 nM) to a final concentration of 65 × 106  sperm/ml. After thawing (0 and 3 hr), we assessed the following sperm traits: sperm motility by computer-assisted sperm analysis (CASA), DNA fragmentation index by SCSA® and plasma and acrosome membrane integrity, intracellular calcium concentration, esterase activity, mitochondrial membrane potential and synthesis of ROS using two multicolour flow cytometric assays. After 3 hr of incubation, 20 nM MitoQ increased (p < .05) sperm ROS synthesis compared to Control, whereas none of the other quality parameters were altered (p > .05). Therefore, we concluded that addition of MitoQ to semen extender before cryopreservation of bull sperm was unable to improve post-thaw sperm quality. Furthermore, 20 nM of MitoQ increased frozen-thawed sperm ROS synthesis, without apparent negative effects on the evaluated sperm traits.

Effects of Combined Treatment with Compounds Affecting Mitochondria on Physiological Parameters in Old Monkey.

Correction of mitochondrial function is a promising direction for modulating aging processes. The effect of NAD+ (in the form of its precursor nicotinamide mononucleotide, NMN) and antioxidant MitoQ specifically affecting mitochondria was studied on male rhesus monkeys (Macaca mulatta). The first group of animals initially received only NMN, the second group received only MitoQ, and then both groups received both drugs simultaneously. The above treatment did not lead to changes in the body weight and body temperature, hemostasis, and ECG. The use of MitoQ, but not NMN improved some hematological and biochemical parameters, shifting them to the values of young animals. Changes in these parameters depended on animal age, so the use of MitoQ can only be effective until a certain age. Combined use of the two drugs had no clear advantages over MitoQ alone.

Placental treatment improves cardiac tolerance to ischemia/reperfusion insult in adult male and female offspring exposed to prenatal hypoxia.

Offspring born from complicated pregnancies are at greater risk of cardiovascular disease in adulthood. Prenatal hypoxia is a common pregnancy complication that results in placental oxidative stress and impairs fetal development. Adult offspring exposed to hypoxia during fetal life are more susceptible to develop cardiac dysfunction, and show decreased cardiac tolerance to an ischemia/reperfusion (I/R) insult. To improve offspring cardiac outcomes, we have assessed the use of a placenta-targeted intervention during hypoxic pregnancies, by encapsulating the mitochondrial antioxidant MitoQ into nanoparticles (nMitoQ). We hypothesized that maternal nMitoQ treatment during hypoxic pregnancies improves cardiac tolerance to I/R insult in adult male and female offspring. Pregnant Sprague-Dawley rats were exposed to normoxia (21 % O2) or hypoxia (11 % O2) from gestational day 15-20, after injection with 100 µL saline or nMitoQ (125 µM) on GD15 (n=6-8/group). Male and female offspring were aged to 4 months. Both male and female offspring from hypoxic pregnancies showed reduced cardiac tolerance to I/R (assessed ex vivo using the isolated working heart technique) which was ameliorated by nMitoQ treatment. To identify potential molecular mechanisms for the changes in cardiac tolerance to I/R, cardiac levels/phosphorylation of proteins important for intracellular Ca2+ cycling were assessed with Western blotting. In prenatally hypoxic male offspring, improved cardiac recovery from I/R by nMitoQ was accompanied by increased cardiac phospholamban and phosphatase 2Ce levels, and a trend to decreased Ca2+/calmodulin-dependent protein kinase IIδ phosphorylation. In contrast, in female offspring, nMitoQ treatment in hypoxic pregnancies increased phospholamban and protein kinase Cε phosphorylation. Maternal nMitoQ treatment improves cardiac tolerance to I/R insult in adult offspring and thus has the potential to improve the later-life trajectory of cardiovascular health of adult offspring born from pregnancies complicated by prenatal hypoxia.

MitoQ protects against high glucose-induced brain microvascular endothelial cells injury via the Nrf2/HO-1 pathway.

Brain microvascular endothelial cells (BMECs) dysfunction is related to the pathogenesis of neurovascular complication of diabetes mellitus that adversely lead to various CNS disorders. Mitoquinone (MitoQ) is a mitochondria targeted antioxidant that exerts multiple protective effects in many oxidative damage-related diseases. In this study, we determined the protective effects of MitoQ on high glucose (HG)-induced BMECs injury and investigated the underlying mechanism. We found that HG significantly reduced the expression of Nrf2 and HO-1, decreased mitochondrial membrane potential, increased intracellular and mitochondrial reactive oxygen species (ROS) generation, induced cytoskeletal damage and apoptosis in BMECs. In addition, Mito tempol, a mitochondrial ROS scavenger, significantly reduced HG-induced mitochondrial ROS production and attenuated cytoskeletal damage and cell apoptosis, suggesting MtROS production was involved in HG-induced BMECs injury. Moreover, we found that MitoQ treatment significantly upregulated the expression of Nrf2 and HO-1 in HG-induced BMECs, which is accompanied by improved mitochondrial membrane potential and decreased MtROS production. Meanwhile, MitoQ treatment also remarkably attenuated HG-induced cytoskeletal damage and cell apoptosis in BMECs. However, inhibitor of Nrf2 with ML385 impaired the protective effects of MitoQ in HG-induced BMECs. In conclusion, our results suggest that MitoQ exerts protective effect on HG-induced BMECs injury via activating Nrf2/HO-1 pathway.

The effect of Mitoquinol (MitoQ) on heat stressed skeletal muscle from pigs, and a potential confounding effect of biological sex.

Heat stress (HS) poses a major threat to human health and agricultural production. Oxidative stress and mitochondrial dysfunction appear to play key roles in muscle injury caused by HS. We hypothesized that mitoquinol (MitoQ), would alleviate oxidative stress and cellular dysfunction in skeletal muscle during HS. To address this, crossbred barrows (male pigs) were treated with placebo or MitoQ (40 mg/d) and were then exposed to thermoneutral (TN; 20 °C) or HS (35 °C) conditions for 24 h. Pigs were euthanized following the environmental challenge and the red portion of the semitendinosus (STR) was collected for analysis. Unexpectedly, malondialdehyde concentration, an oxidative stress marker, was similar between environmental and supplement treatments. Heat stress decreased LC3A/B-I (p < 0.05) and increased the ratio of LC3A/B-II/I (p < 0.05), while p62 was similar among groups suggesting increased degradation of autophagosomes during HS. These outcomes were in disagreement with our previous results in muscle from gilts (female pigs). To probe the impact of biological sex on HS-mediated injury in skeletal muscle, we compared STR from these barrows to archived STR from gilts subjected to a similar environmental intervention. We confirmed our previous findings of HS-mediated dysfunction in muscle from gilts but not barrows. These data also raise the possibility that muscle from gilts is more susceptible to environment-induced hyperthermia than muscle from barrows.

Self-Associating Polymers Chitosan and Hyaluronan for Constructing Composite Membranes as Skin-Wound Dressings Carrying Therapeutics.

Chitosan, industrially acquired by the alkaline N-deacetylation of chitin, belongs to ß-N-acetyl-glucosamine polymers. Another ß-polymer is hyaluronan. Chitosan, a biodegradable, non-toxic, bacteriostatic, and fungistatic biopolymer, has numerous applications in medicine. Hyaluronan, one of the major structural components of the extracellular matrix in vertebrate tissues, is broadly exploited in medicine as well. This review summarizes that these two biopolymers have a mutual impact on skin wound healing as skin wound dressings and carriers of remedies.

Pro- and antitumor effects of mitochondrial reactive oxygen species.

In cancer, mitochondrial functions are commonly altered. Directly involved in metabolic reprogramming, mitochondrial plasticity confers to cancer cells a high degree of adaptability to a wide range of stresses and to the harsh tumor microenvironment. Lack of nutrients or oxygen caused by altered perfusion, metabolic needs of proliferating cells, co-option of the microenvironment, control of the immune system, cell migration and metastasis, and evasion of exogenous stress (e.g., chemotherapy) are all, at least in part, influenced by mitochondria. Mitochondria are undoubtedly one of the key contributors to cancer development and progression. Understanding their protumoral (dys)functions may pave the way to therapeutic strategies capable of turning them into innocent entities. Here, we will focus on the production and detoxification of mitochondrial reactive oxygen species (mtROS), on their impact on tumorigenesis (genetic, prosurvival, and microenvironmental effects and their involvement in autophagy), and on tumor metastasis. We will also summarize the latest therapeutic approaches involving mtROS.