Hyperbaric oxygen therapy restores wound healing in irradiated gingiva to a similar level to that in healthy gingiva.

OBJECTIVE: This study aimed to investigate the involvement of mitochondrial biogenesis, and determine the extent of fibroblast proliferation and cellular apoptosis, in the gingiva of patients who had undergone head and neck radiation, after receiving hyperbaric oxygen therapy (HBOT), in comparison with normal gingiva. METHOD: A total of 16 patients who had undergone head and neck radiation with HBOT and six healthy subjects were included in the study. After the completion of radiation therapy, patients received HBOT at 2 ATA for 90 minutes per session, and for 20 sessions per patient. Samples of gingival tissues were then taken. The levels of: transforming growth factor beta (TGF-ß); phospho-nuclear factor kappa-light-chain-enhancer of activated B cells (p-NFÏ°B); nuclear factor kappa-light-chain-enhancer of activated B cells (NFÏ°B); proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α); phospho-dynamin-related protein 1 at ser616 (p-Drp1ser616); dynamin-related protein 1 (Drp1); Bcl-2-associated X-protein (Bax); and B-cell lymphoma 2 (Bcl-2) were determined using a Western blot. Independent t-test and Chi-squared tests were used in the study. RESULTS: There were no differences in the levels of TGF-ß, p-NFÏ°B, NFÏ°B, p-Drp1ser616, Drp1, Bax and Bcl-2 between the two groups. However, the level of PGC-1α was greater in irradiated gingival tissues with HBOT than in the healthy gingiva. CONCLUSION: Radiation-induced impaired wound healing can be improved by HBOT as indicated by levels of apoptosis, mitochondrial dynamics, cell proliferation and inflammation in irradiated gingiva with HBOT to a similar level to normal healthy gingiva. These findings may occur through an increase in mitochondrial biogenesis following HBOT.

Acute administration of myeloid differentiation factor 2 inhibitor and N-acetyl cysteine attenuate brain damage in rats with cardiac ischemia/reperfusion injury.

Inflammation and oxidative stress are mechanisms which potentially underlie the brain damage that can occur after cardiac ischemic and reperfusion (I/R) injury. 2i-10 is a new anti-inflammatory agent, acting via direct inhibition of myeloid differentiation factor 2 (MD2). However, the effects of 2i-10 and the antioxidant N-acetylcysteine (NAC) on pathologic brain in cardiac I/R injury are unknown. We hypothesized that 2i-10 and NAC offer similar neuroprotection levels against dendritic spine reduction through attenuation of brain inflammation, loss of tight junction integrity, mitochondrial dysfunction, reactive gliosis, and suppression of AD protein expression in rats with cardiac I/R injury. Male rats were allocated to either sham or acute cardiac I/R group (30 min of cardiac ischemia and 120 min of reperfusion). Rats in cardiac I/R group were given one of following treatments intravenously at the onset of reperfusion: vehicle, 2i-10 (20 or 40 mg/kg), and NAC (75 or 150 mg/kg). The brain was then used to determine biochemical parameters. Cardiac I/R led to cardiac dysfunction with dendritic spine loss, loss of tight junction integrity, brain inflammation, and mitochondrial dysfunction. Treatment with 2i-10 (both doses) effectively reduced cardiac dysfunction, tau hyperphosphorylation, brain inflammation, mitochondrial dysfunction, dendritic spine loss, and improved tight junction integrity. Although both doses of NAC effectively reduced brain mitochondrial dysfunction, treatment using a high dose of NAC reduced cardiac dysfunction, brain inflammation, and dendritic spine loss. In conclusion, treatment with 2i-10 and a high dose of NAC at the onset of reperfusion alleviated brain inflammation and mitochondrial dysfunction, consequently reducing dendritic spine loss in rats with cardiac I/R injury.

Corrigendum to "Effect of intensive weekend mindfulness-based intervention on BDNF, mitochondria function, and anxiety. A randomized, crossover clinical trial" [Compr. Psychoneuroendocrinol. (2022) 100137].

[This corrects the article DOI: 10.1016/j.cpnec.2022.100137.].

Effect of intensive weekend mindfulness-based intervention on BDNF, mitochondria function, and anxiety. A randomized, crossover clinical trial.

Background: The previous metanalysis found that Mind-body intervention (MBI) improves neuropsychologic well-being and may increase brain-derived growth factor (BDNF). BDNF is a neurotrophic factor related to neuroplasticity. Objective: To evaluate the effect of the short intensive MBI compared to control-relaxation on Site on BDNF and examine if this change is related to mitochondria function or stress-related neurohormonal activity. Methods: Randomized, controlled, two-period cross-over trial conducted in a medical center in Thailand. Healthy-meditation naive Nurse and Occupational Therapy Students, 23 assigned randomly to MBI, and 24 relaxations at the site for 8 h during the weekend. The wash-out period was three months between the two periods. All volunteers took the blood test for BDNF, mitochondrial oxidative phosphorylation (OXPHOS), Cortisol, and Heart rate variability (HRV) measurement before and Visual Analogue Scale for Anxiety (VAS-A), forward and backward digit span after each period. Results: A total of 40 participants finished the trials. The cross over trial analysis showed a significant treatment effect between MBI and Relaxation on-site for the mean VAS-A as 9.89 (95% CI 4.81 to 19.47; P = 0.001), serum BDNF as 1.24 (95% CI 0.16 to 2.32; P = 0.04), and OXPHOS complex-1 was decreased 0.41 (95% CI 0.03-0.29 p = 0.03). There were no significant differences for digit span, cortisol, and HRV. Conclusion: In healthy meditation naïve females, even a short period of MBI may increase serum BDNF and reduce anxiety more than relaxation on-site. The more reduction of OXPHOS complex-1 in the mindfulness group suggests oxidative stress may be a more sensitive indicator than stress-related neurohormonal activity.

Neurotensin receptor 1 agonist provides neuroprotection in pre-diabetic rats.

Exogenous treatment of a neurotensin receptor 1 (NTR1) agonist exerted the neuroprotection in an obese and Alzheimer's model. However, the effects of NTR1 modulation on peripheral/hippocampal impairment and cognitive deficit following sustained HFD consumption are poorly understood. Forty rats received a normal diet (ND) or HFD for 16 weeks. At week 13, the ND group received a vehicle (n = 8). Thirty-two HFD-fed group were randomized into four subgroups (n = 8/subgroup) with a vehicle, 1 mg/kg of NTR1 agonist, 1 mg/kg of NTR antagonist, and combined treatment (NTR1 agonist-NTR antagonist) for 2 weeks, s.c. injection. Then, the cognitive tests and peripheral/hippocampal parameters were determined. Our findings demonstrated that NTR1 activator reversed obesity and attenuated metabolic impairment in pre-diabetic rats. It also alleviated hippocampal pathologies and synaptic dysplasticity, leading to deceleration or prevention of cognitive impairment progression. Therefore, NTR1 activation would be a possible novel therapy to decelerate or prevent progression of neuropathology and cognitive impairment in the pre-diabetes.

The comparative effects of high dose atorvastatin and proprotein convertase subtilisin/kexin type 9 inhibitor on the mitochondria of oxidative muscle fibers in obese-insulin resistant female rats.

The present study aimed to compare the effects of high dose atorvastatin and a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor on the mitochondrial function in oxidative muscle fibers in obese female rats. Female Wistar rats were fed with either a normal diet (ND: n = 12) or a high-fat diet (HFD: n = 36) for a total of 15 weeks. At week 13, ND-fed rats received a vehicle, and HFD-fed rats were divided to three groups to receive either a vehicle, 40 mg/kg/day of atorvastatin, or 4 mg/kg/day of PCSK9 inhibitor (SBC-115076) for 3 weeks. Soleus muscles were investigated to assess mitochondrial ROS, membrane potential, swelling, mitochondrial-related protein expression, and level of malondialdehyde (MDA). The results showed that HFD-fed rats with vehicle developed obese-insulin resistance and dyslipidemia. Both atorvastatin and PCSK9 inhibitor reduced obesity and dyslipidemia, as well as improved insulin sensitivity in HFD-fed rats. However, the efficacy of PCSK9 inhibitor to increase weight loss and reduce dyslipidemia in HFD-fed rats was greater than those of atorvastatin. An increase in MDA level, ratio of p-Drp1ser616/total Drp1 protein, CPT1 protein, mitochondrial ROS, and membrane depolarization in the soleus muscle were observed in HFD-fed rats with vehicle. PCSK9 inhibitor enabled the restoration of all these parameters to normal levels. However, atorvastatin facilitated restoration of some parameters, including MDA level, p-Drp1ser616/total Drp1 ratio, and CPT1 protein expression. These findings suggest that PCSK9 inhibitor is superior to atorvastatin in instigating weight loss, cholesterol reduction, and attenuation of mitochondrial oxidative stress in oxidative muscle fibers of obese female rats.

Coenzyme Q10 supplementation alleviates pain in pregabalin-treated fibromyalgia patients via reducing brain activity and mitochondrial dysfunction.

Although coenzyme Q10 (CoQ10) supplementation has shown to reduce pain levels in chronic pain, the effects of CoQ10 supplementation on pain, anxiety, brain activity, mitochondrial oxidative stress, antioxidants, and inflammation in pregabalin-treated fibromyalgia (FM) patients have not clearly elucidated. We hypothesised that CoQ10 supplementation reduced pain better than pregabalin alone via reducing brain activity, mitochondrial oxidative stress, inflammation, and increasing antioxidant levels in pregabalin-treated FM patients. A double-blind randomised placebo-controlled trial was conducted. Eleven FM patients were enrolled with 2 weeks wash-out then randomly allocated to 2 treatment groups; pregabalin with CoQ10 or pregabalin with placebo for 40 d. Then, patients in CoQ10 group were switched to placebo, and patients in placebo group were switched to CoQ10 for another 40 d. Pain pressure threshold (PPT), FM questionnaire, anxiety, and pain score were examined. Peripheral blood mononuclear cells (PBMCs) were isolated to investigate mitochondrial oxidative stress and inflammation at day 0, 40, and 80. The level of antioxidants and brain positron emission tomography (PET) scan were also determined at these time points. Pregabalin alone reduced pain and anxiety via decreasing brain activity compared with their baseline. However, it did not affect mitochondrial oxidative stress and inflammation. Supplementation with CoQ10 effectively reduced greater pain, anxiety and brain activity, mitochondrial oxidative stress, and inflammation. CoQ10 also increased a reduced glutathione levels and superoxide dismutase (SOD) levels in FM patients. These findings provide new evidence that CoQ10 supplementation provides further benefit for relieving pain sensation in pregabalin-treated FM patients, possibly via improving mitochondrial function, reducing inflammation, and decreasing brain activity.

Effect of coenzyme Q10 on mitochondrial respiratory proteins in trigeminal neuralgia.

Trigeminal neuralgia (TN) is the neuropathic pain. Mitochondrial dysfunction, increased oxidative stress, and inflammation demonstrated in chronic pain. Carbamazepine (CBZ) is the first-line drug for TN, however, it is still insufficient. Coenzyme Q10 (CoQ10) has been used as the additional supplement for pain therapy. Nonetheless, mitochondrial respiratory proteins, oxidative stress, and inflammation in TN, and the add-on effects of CoQ10 on those defects have never been investigated. CBZ-treated TN-patients, naïve TN-patients, and control subjects were included. CBZ-treated TN-patients were randomised into two subgroups, received either CoQ10 or placebo for 2 months. Pain levels were evaluated, and peripheral blood mononuclear cells were isolated to determine the oxidative stress, mitochondrial oxidative phosphorylation (OXPHOS), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), and cytokines including TNF-α, IL-1ß and IL-18 mRNA expression. Pain scales, oxidative stress, and OXPHOS levels were greater in naïve TN-patients than control, whereas the cytokine profiles were unchanged. Although pain scales were lower in CBZ-treated TN-patients than in naïve TN-patients, oxidative stress, OXPHOS, and cytokine expression profiles were not different. PGC-1α levels found to be increased in CBZ-treated TN patients when compared with the naïve group. CoQ10 supplement in CBZ-treated TN patients reduced pain scale and oxidative stress and increased antioxidants levels when compared with placebo group. However, OXPHOS, PGC-1α, and cytokines were not different between groups. These findings suggest that increased oxidative stress could be potentially involved in the pathogenesis of TN. CoQ10 supplements can reduce oxidative stress, leading to more effective pain reduction in TN patients being treated with CBZ.

Garlic extract attenuates brain mitochondrial dysfunction and cognitive deficit in obese-insulin resistant rats.

Oxidative stress in the obese-insulin resistant condition has been shown to affect cognitive as well as brain mitochondrial functions. Garlic extract has exerted a potent antioxidant effect. However, the effects of garlic extract on the brain of obese-insulin resistant rats have never been investigated. We hypothesized that garlic extract improves cognitive function and brain mitochondrial function in obese-insulin resistant rats induced by long-term high-fat diet (HFD) consumption. Male Wistar rats were fed either normal diet or HFD for 16 weeks (n = 24/group). At week 12, rats in each dietary group received either vehicle or garlic extract (250 and 500 mg·kg(-1)·day(-1)) for 28 days. Learning and memory behaviors, metabolic parameters, and brain mitochondrial function were determined at the end of treatment. HFD led to increased body weight, visceral fat, plasma insulin, cholesterol, and malondialdehyde (MDA) levels, indicating the development of insulin resistance. Furthermore, HFD rats had cognitive deficit and brain mitochondrial dysfunction. HFD rats treated with both doses of garlic extract had decreased body weight, visceral fat, plasma cholesterol, and MDA levels. Garlic extract also improved cognitive function and brain mitochondrial function, which were impaired in obese-insulin resistant rats caused by HFD consumption.

Protective effects of garlic extract on cardiac function, heart rate variability, and cardiac mitochondria in obese insulin-resistant rats.

PURPOSE: Garlic has been shown to exhibit antioxidant effects and cardioprotective properties. However, the effects of garlic extract on the heart in insulin resistance induced by long-term high-fat-diet consumption are not well defined. Therefore, we sought to determine the effects of garlic extract in the obese insulin-resistant rats. METHODS: Male Wistar rats (180-200 g) were divided into two groups: normal-diet or high-fat-diet (n = 24/group) fed for 12 weeks. Rats in each groups were divided into three subgroups (n = 8 each): vehicle or garlic extract (250 or 500 mg/kg/day, respectively) treated for 28 days. At the end of the treatment, the metabolic parameters, heart rate variability (HRV), cardiac function, and cardiac mitochondrial function were determined. RESULTS: Rats that received a high-fat-diet for 12 weeks had increased body weight, visceral fat, plasma insulin levels, total cholesterol, oxidative stress levels, depressed HRV, and cardiac mitochondrial dysfunction. Garlic extract at both concentrations significantly decreased the plasma insulin, total cholesterol, homeostasis model assessment index, and oxidative stress levels. Furthermore, garlic extract at both doses restored the HRV, cardiac function, and cardiac mitochondrial function. CONCLUSION: We concluded that garlic extract at both concentrations exerted cardioprotective effects against cardiac dysfunction and mitochondrial dysfunction in obese insulin-resistant rats.

Effects of curcuminoids on frequency of acute myocardial infarction after coronary artery bypass grafting.

It is well established that myocardial infarction (MI) associated with coronary artery bypass grafting (CABG) predicts a poor outcome. Nevertheless, cardioprotective therapies to limit myocardial injury after CABG are lacking. Previous studies have shown that curcuminoids decrease proinflammatory cytokines during cardiopulmonary bypass surgery and decrease the occurrence of cardiomyocytic apoptosis after cardiac ischemia/reperfusion injury in animal models. We aimed to evaluate whether curcuminoids prevent MI after CABG compared to placebo. The 121 consecutive patients undergoing CABG were randomly allocated to receive placebo or curcuminoids 4 g/day beginning 3 days before the scheduled surgery and continued until 5 days after surgery. The primary end point was incidence of in-hospital MI. The secondary end point was the effect of curcuminoids on C-reactive protein, plasma malondialdehyde, and N-terminal pro-B-type natriuretic peptide levels. Baseline characteristics were comparable between the curcuminoid and placebo groups. Mean age was 61 ± 9 years. On-pump CABG procedures were performed in 51.2% of patients. Incidence of in-hospital MI was decreased from 30.0% in the placebo group to 13.1% in the curcuminoid group (adjusted hazard ratio 0.35, 0.13 to 0.95, p = 0.038). Postoperative C-reactive protein, malondialdehyde, and N-terminal pro-B-type natriuretic peptide levels were also lower in the curcuminoid than in the placebo group. In conclusion, we demonstrated that curcuminoids significantly decreased MI associated with CABG. The antioxidant and anti-inflammatory effects of curcuminoids may account for their cardioprotective effects shown in this study.