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SUMMARY: The aim of this study was to evaluate the hard and soft tissue profile changes following treatment of functional and mild skeletal class III malocclusion in mixed dentition by means of the Frankel functional regulator (FR-3) appliance, and to reveal the mechanism and effectiveness of treatment with FR-3 appliance. Twenty-six patients (chronological mean age, 8.7±1.4 years; mean treatment duration, 10.3±1.3 months) with functional and mild skeletal class III malocclusion were selected and treated with FR-3 appliances. Lateral cephalogram was taken pre- and post-treatment, and the data was analyzed by paired-samples t test with SPSS22.0 software package. Differences were considered statistically significant at P < 0.05. The results demonstrated that the FR-3 appliance produced a statistically significant decrease in L1-NB, L1-MP, U1-L1 (P

Many neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease, are associated with microvascular dysfunction, but the cellular and molecular mechanisms are poorly understood. Recently, microRNAs (miRNAs) have been suggested to be involved in the microvascular dysfunction and subsequent memory impairment. MicroRNA-124 (miR-124) is one of the most abundant miRNAs in the brain that is dysregulated in the hippocampus of AD animals. To explore the role of miR-124 in AD pathology, we employed the APP/PS1 transgenic mice and found downregulation of miR-124 and upregulation of complement C1q-like protein 3 (C1ql3) in the hippocampus and cerebral cortex. Downregulation of miR-124 expression resulted in Aβ deposition and a variety of cerebromicrovascular impairments, including the decline in microvascular density, reduced angiogenesis, accompanied by C1ql3 alteration. Treatment with lentivirus-mediated overexpression of miR-124 or the C1q inhibitor C1INH rescued breakdown of blood-brain barrier, promoted angiogenesis and reduced Aβ deposition, and finally alleviated learning and memory deficit in APP/PS1 mice. Moreover, we found that C1ql3, a component of the classical complement, might be a potential target of miR-124. These results suggested that miR-124 was involved in the angiogenesis and vascular integrity in the hippocampus and the cerebral cortex of the AD mice by regulating the classical complement C1ql3.

A new species of the genus Mongolotettix Rehn, 1928 from Henan, China is described. The new species, Mongolotettix tongbaishanensis Yin, Ji et Dai sp. n. is similar to M. shanxiensis Shi, Liu et Li, 2016, but differs from the latter by shorter tegmina of male, which reach the hind margin of the 6th abdominal tergite, the maximumwidth of cubital area being 1.2 times wider than the maximum width of the medial area, the prozona of male being 1.5 times longer than the metazona, the tegmina of female being short, extending slightly over the hind margin of the 1st abdominal tergite, the length of tegmina being 2.5 times longer than its maximum width, the epiphallus being wider than high, and the length of the upper ovipositor valve being 4.4 times longer than its maximum width.

Background Pistachio (Pistacia vera), one of the most important commercial nut crops worldwide, is highly adaptable to abiotic stresses and is tolerant to drought and salt stresses. Results Here, we provide a draft de novo genome of pistachio as well as large-scale genome resequencing. Comparative genomic analyses reveal stress adaptation of pistachio is likely attributable to the expanded cytochrome P450 and chitinase gene families. Particularly, a comparative transcriptomic analysis shows that the jasmonic acid (JA) biosynthetic pathway plays an important role in salt tolerance in pistachio. Moreover, we resequence 93 cultivars and 14 wild P. vera genomes and 35 closely related wild Pistacia genomes, to provide insights into population structure, genetic diversity, and domestication. We find that frequent genetic admixture occurred among the different wild Pistacia species. Comparative population genomic analyses reveal that pistachio was domesticated about 8000 years ago and suggest that key genes for domestication related to tree and seed size experienced artificial selection. Conclusions Our study provides insight into genetic underpinning of local adaptation and domestication of pistachio. The Pistacia genome sequences should facilitate future studies to understand the genetic basis of agronomically and environmentally related traits of desert crops. Electronic supplementary material The online version of this article (10.1186/s13059-019-1686-3) contains supplementary material, which is available to authorized users.

Sarcopenia, the age-related decline in muscle mass and function, derives from multiple etiological mechanisms. Accumulative research suggests that reactive oxygen species (ROS) generation plays a critical role in the development of this pathophysiological disorder. In this communication, we review the various signaling pathways that control muscle metabolic and functional integrity such as protein turnover, cell death and regeneration, inflammation, organismic damage, and metabolic functions. Although no single pathway can be identified as the most crucial factor that causes sarcopenia, age-associated dysregulation of redox signaling appears to underlie many deteriorations at physiological, subcellular, and molecular levels. Furthermore, discord of mitochondrial homeostasis with aging affects most observed problems and requires our attention. The search for the primary suspect of the fundamental mechanism for sarcopenia will likely take more intense research for the secret of this health hazard to the elderly to be unlocked.

Objective To investigate the mechanisms of andrographolide against non-alcoholic steatohepatitis (NASH) based on network pharmacology, so as to provide a reference for further study of andrographolide in the treatment of NASH and other metabolic diseases. Methods The methionine- and choline-deficient (MCD) diet-induced NASH mice were treated by administration of andrographolide, and serum transaminase and pathological changes were analyzed. The network pharmacology-based bioinformatic strategy was then used to search the potential targets, construct protein–protein interaction (PPI) network, analyze gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment, and conduct molecular docking to explore the molecular mechanisms. Results The predicted core targets TNF, MAPK8, IL6, IL1B and AKT1 were enriched in non-alcoholic fatty liver disease (NAFLD) signaling pathway and against NASH by regulation of de novo fatty acids synthesis, anti-inflammation and anti-oxidation. Conclusion This work provides a scientific basis for further demonstration of the anti-NASH mechanisms of andrographolide.

MicroRNA-142-5p (miR-142-5p) has been found to be dysregulated in several neurodegenerative disorders. However, little is known about the involvement of miR-142-5p in Alzheimer's disease (AD). Brain angiogenesis inhibitor 3 (BAI3), which belongs to the adhesion-G protein-coupled receptor subgroup, contributes to a variety of neuropsychiatric disorders. Despite its very high expression in neurons, the role of BAI3 in AD remains elusive, and its mechanism at the cellular and molecular levels needs to be further elucidated. The current study sought to investigate whether miR-142-5p influenced BAI3 expression and neuronal synaptotoxicity induced by Aβ, both in APP/PS1 transgenic mice and a cellular model of Alzheimer's disease. Altered expression of miR-142-5p was found in the hippocampus of AD mice. Inhibition of miR-142 could upregulate BAI3 expression, enhance neuronal viability and prevent neurons from undergoing apoptosis. In addition, the reduction of phosphorylation of Synapsin I and calcium/calmodulin-dependent protein kinase II (CaMKII), as well as the expression of PSD-95 in the hippocampus of APP/PS1 transgenic mice, were significantly restored by inhibiting miR-142. Meanwhile, the levels of Aβ1-42, β-APP, BACE-1 and PS-1 in cultured neurons were detected, and the effects of inhibiting miR-142 on spatial learning and memory were also observed. Interestingly, we found that BAI3, an important regulator of excitatory synapses, was a potential target gene of miR-142-5p. Collectively, our findings suggest that miR-142 inhibition can alleviate the impairment of spatial learning and memory, reduce the level of apoptosis, and upregulate the expression of pCaMKII and BAI3 in the hippocampus of APP/PS1 transgenic mice; thus, appropriate interference of miR-142 may provide a potential therapeutic approach to rescue cognitive dysfunction in AD patients.

Accumulating evidence has demonstrated that the σ-1 receptor (σ‑1R) possesses neuroprotective effects and is a potential novel therapeutic target for certain psychiatric diseases, including post‑traumatic stress disorder (PTSD) accompanied with anxiety disorder. It has been reported that σ‑1R agonist treatment could be modulated by the brain‑derived neurotrophic factor (BDNF) signaling pathway. However, it remains unclear whether BDNF and its upstream regulator are mechanistically involved in the therapeutic effect of σ‑1R in PTSD. To address this question, rats were subjected to a single‑prolonged stress (SPS) paradigm and σ‑1R agonist administration. Open‑field and elevated plus maze tests were implemented to evaluate the effect of σ‑1R activation on the improvement of anxiety‑like behaviors. Furthermore, the expression levels of BDNF, phosphorylated cAMP responsive element‑binding protein (CREB) and glutamate receptor ionotropic N‑methyl D‑aspartate 2A (NMDAR2A) were investigated in the hippocampi of rats. It was revealed that the downregulation of BDNF, phosphorylated CREB and NMDAR2A induced by SPS were reversed by σ‑1R activation. Collectively, the results of the present study suggest that the NMDAR2A/CREB/BDNF signaling pathway is involved in the activation of σ‑1R resulting in therapeutic effects for PTSD.

Cognitive impairment in Alzheimer’s disease (AD) is usually accompanied by synaptic loss in both the hippocampus and neocortex. In the early stage of AD, amyloid β-induced synapse changes is the main reason, while in the later stage, the accumulation of Tau protein promotes synapse degeneration as the key factor leading to dementia. MicroRNA (miRNA) is closely related to the expression changes of many AD-related genes. One of the most abundant brain-enriched miRNAs is miR-132, which has been shown to regulate both neuron morphogenesis and plasticity. It has been reported that miR-132 is significantly reduced in the brains of Alzheimer’s patients. Genetic deletion of miR-132 in mice promotes Aβ deposition, leading to impaired memory and enhanced Tau pathology, but how the miRNA-mediated gene expression dysregulation contributes to AD pathology remains unclear. Here we found the possible downstream target of miR-132 by in silico analysis, namely C1q. C1q is the primary protein of classical complement cascade, which is highly expressed in the synaptic regions of the central nervous system in Alzheimer’s patients. However, it is not clear whether miR-132 plays a role in AD through regulating C1q. To address this question, the APP/PS1 transgenic mice were transfected with miR-132 and given C1 inhibitors. Behavior tests were conducted to assess memory and cognitive abilities seven days after administration. In addition, we analyzed the expression of PSD95, Synapsin-1 and phosphorylated (p)-Synapsin. We found that the expression levels of the synaptic proteins treated with miR-132 or C1INH were significantly increased compared with the AD group. Further RT-qPCR result suggested that miR-132 might regulate C1q expression in AD.

To investigate the effect of electroacupuncture (EA) treatment on the expression of cyclooxygenase (COX) 2 and microglia in spinal cord by using rat model of neuropathic pain, and to probe into the relationship between COX 2 and microglia. The rats were randomly divided into 6 groups, including normal control group, model group, sham group, EA 1 group (distant acupoints + local acupoints), EA 2 group (local acupoints), and EA 3 group (distant acupoints). Thermal withdrawal latencies were evaluated at 1 day preoperatively and 3, 5 and 7 days postoperatively. At 7 days postoperatively, the spinal COX 2 mRNA was detected by reverse-transcription polymerase chain reaction. Double immunofluorescent staining technology was applied to screen and verify the relationship between altered COX 2 and microglia. Compared with the model group, thermal withdrawal latencies increased after EA treatment (P

Hormesis refers to the phenomenon that an exposure or repeated exposures of a toxin can elicit adaptive changes within the organism to resist to higher doses of toxin with reduced harm. Skeletal muscle shows considerable plasticity and adaptions in response to a single bout of acute exercise or chronic training, especially in antioxidant defense capacity and metabolic functions mainly due to remodeling of mitochondria. It has thus been hypothesized that contraction-induced production of reactive oxygen species (ROS) may stimulate the hormesis-like adaptations. Furthermore, there has been considerable evidence that select ROS such as hydrogen peroxide and nitric oxide, or even oxidatively degraded macromolecules, may serve as signaling molecules to stimulate such hermetic adaptations due to the activation of redox-sensitive signaling pathways. Recent research has highlighted the important role of nuclear factor (NF) κB, mitogen-activated protein kinase (MAPK), and peroxisome proliferator-activated receptor γ co-activator 1α (PGC-1α), along with other newly discovered signaling pathways, in some of the most vital biological functions such as mitochondrial biogenesis, antioxidant defense, inflammation, protein turnover, apoptosis, and autophagy. The inability of the cell to maintain proper redox signaling underlies mechanisms of biological aging, during which inflammatory and catabolic pathways prevail. Research evidence and mechanisms connecting exercise-induced hormesis and redox signaling are reviewed.

A new species of the genus Confusacris Yin & Li, 1987, namely i.e. Confusacris shanxiensis sp. nov. is described in this paper from Shanxi province of China. The new species is similar to Confusacris brachypterus Yin & Li, 1987 but differs from the latter by tegmen of male extending over middle of hind femur distinctly, maximum width of cubital vein area 1.5 times median vein area, furculae large, epiphallus without acute projection on both sides and length of interspace of mesosternum1.6 times minimum width in female. A key to known species of the genus Confusacris Yin & Li, 1987 is given in this paper. The type specimens are deposited in the College of Life Sciences, Hebei University, Baoding, China.

Acetaminophen (APAP) is a well-known antipyretic and analgesic drug. However, the accidental or intentional APAP overdose will induce liver injury and even acute liver failure. Astragaloside IV (AS-IV), a bioactive compound isolated from Astragali Radix, has been reported to have protective effects on the digestive and immune systems because of its anti-oxidant and anti-inflammatory properties. This study aims to observe whether AS-IV pretreatment provides protection against APAP-induced liver failure. The results of serum alanine/aspartate aminotransferases (ALT/AST) analysis, hepatic glutathione (GSH), and malondialdehyde (MDA) amounts, and liver superoxide dismutase (SOD) activity showed that AS-IV protected against APAP-induced hepatotoxicity. Liver histological observation further evidenced this protection provided by AS-IV. AS-IV was found to reverse the APAP-induced increased amounts of pro-inflammatory cytokines, including interleukin 1&beta, (IL-1&beta, ), interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-&alpha, ). Western-blot analysis showed that AS-IV increased the transcriptional activation of nuclear factor erythroid 2-related factor 2 (Nrf2), and enhanced the expression of heme oxygenase 1 (HO-1) and reduced nicotinamide adenine dinucleotide phosphate (NAD(P)H): quinone oxidoreductase 1 (NQO1) in the presence of APAP. AS-IV also decreased the expression of kelch-like ECH-associated protein-1 (Keap1). In conclusion, we demonstrated that AS-IV exerted a strong protection against APAP-induced hepatotoxicity by activating Nrf2 antioxidant signaling pathways.

Increasing evidence has indicated that acute strenuous exercise can induce a range of adverse reactions including oxidative stress and tissue inflammation. However, little is currently known regarding the mechanisms that underlie the regulation of the inflammatory response in the myocardium during acute heavy exercise. This study evaluated the mitochondrial function, NLRP3 inflammasome activation, and mitochondrial autophagy-related proteins to investigate the regulation and mechanism of mitochondrial stress regarding the inflammatory response of the rat myocardium during acute heavy exercise. The results indicated that the mitochondrial function of the myocardium was adaptively regulated to meet the challenge of stress during acute exercise. The exercise-induced mitochondrial stress also enhanced ROS generation and triggered an inflammatory reaction via the NLRP3 inflammasome activation. Moreover, the mitochondrial autophagy-related proteins including Beclin1, LC3, and Bnip3 were all significantly upregulated during acute exercise, which suggests that mitophagy was stimulated in response to the oxidative stress and inflammatory response in the myocardium. Taken together, our data suggest that, during acute exercise, mitochondrial stress triggers the rat myocardial inflammatory response via NLRP3 inflammasome activation and activates mitophagy to minimize myocardial injury.

Skeletal muscle contraction is associated with the production of ROS due to altered O2distribution and flux in the cell. Despite a highly efficient antioxidant defense, a small surplus of ROS, such as hydrogen peroxide and nitric oxide, may serve as signaling molecules to stimulate cellular adaptation to reach new homeostasis largely due to the activation of redox-sensitive signaling pathways. Recent research has highlighted the important role of NF-κB, MAPK, and peroxisome proliferator-activated receptor-γ coactivator-1α, along with other newly discovered signaling pathways, in some of the most vital biological functions, such as mitochondrial biogenesis, antioxidant defense, inflammation, protein turnover, apoptosis, and autophagy. There is evidence that the inability of the cell to maintain proper redox signaling underlies some basic mechanisms of biological aging, during which inflammatory and catabolic pathways eventually predominate. Physical exercise has been shown to activate various redox signaling pathways that control the adaptation and remodeling process. Although this stimulatory effect of exercise declines with aging, it is not completed abolished. Thus, aged people can still benefit from regular physical activity in the appropriate forms and at proper intensity to preserve muscle function.

Sarcopenia is age-associated deterioration of muscle mass and function caused by a wide scope of physiological and pathological changes ranging from hormonal disorders to loss of subcellular homeostasis. Recent research indicates that mitochondrial dysregulation with advanced age plays a central role in the development of sarcopenia due to the multifactorial functions of this organelle in energy supply, redox regulation, crosstalk with nuclear gene expression and apoptosis. In order to fulfill these roles, it is crucial that mitochondria maintain their own structural and functional integrity through biogenesis, antioxidant defense, fusion/fission dynamics and autophagy (mitophagy). Unfortunately, mitochondria undergo age-associated changes that compromise the above-mentioned properties that eventually contribute to the development of sarcopenia. The peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) is involved in the transcriptional regulation of numerous nuclear and mitochondrial gene products participating in the cellular events that control muscle mass and function. Thus, it is not surprising that maintaining an optimal intracellular PGC-1α level and signaling activity is crucial in protecting the muscle from many degradative and destructive processes, such as proteolysis, oxidative damage, inflammation, uncontrolled autophagy and apoptosis. Physical exercise is a powerful stimulus to PGC-1α expression and signaling. Recent research indicates that PGC-1α-controlled mitochondrial biogenesis is not limited by old age per se and that elderly individuals can still benefit from increased muscular activity in terms of skeletal muscle health that ultimately contributes to quality of life in old age.

Aged skeletal muscle demonstrates declines in muscle mass and deterioration of mitochondrial content and function. Peroxisome proliferator-activated receptor γ co-activator 1α (PGC-1α) plays an important role in promoting muscle mitochondrial biogenesis in response to exercise training, but its role in senescent muscle is not clear. In the present study we hypothesize that a downregulation of the PGC-1α signaling pathway contributes to mitochondrial deterioration in aged muscle whereas endurance training ameliorates the deficits. Three groups of Fischer 344/BNF1 rats were used: young, sedentary (Y, 4 months); old, sedentary (O, 22 months); and old trained (OT, 22 months), subjected to treadmill running at 17.5 m/min, 10% grade for 45 min/day, 5 days/week for 12-weeks. PGC-1α mRNA and nuclear PGC-1α protein content in the soleus muscle were both decreased in O vs. Y rats, whereas OT rats showed a 2.3 and 1.8-fold higher PGC-1α content than O and Y rats, respectively (P

Contraction-induced production of reactive oxygen species (ROS) has been implicated in oxidative stress to skeletal muscle for the past few decades. As research advances more evidence has revealed a more complete role of ROS under both physiological and pathological conditions. The current review postulated that moderate intensity of physical exercise has antioxidant and anti-inflammatory effects due to the operation and cross-talks of several redox-sensitive signal transduction pathways. The functional roles and mechanisms of action of the nuclear factor κB, mitogen-activated protein kinase, and peroxisome proliferator-activated receptor γ co-activator 1α are highlighted.

Mitochondrial redox metabolism has long been recognized as being central to the effects of aging and the development of age-related pathologies in the major oxidative organs. Consistent evidence has shown that exercise is able to retard the onset and impede the progression of aging by modifying mitochondrial oxidant–antioxidant homeostasis. Here we provide a broad overview of the research evidence showing the relationship between mitochondrial redox metabolism, aging and exercise. We address part aspects of mitochondrial reactive oxygen species (ROS) metabolism, from superoxide production to ROS detoxification, especially antioxidant enzymes and uncoupling protein. Furthermore, we describe mitochondrial remodeling response to aging and exercise, which is accompanied by bioenergetics and redox regulation. In addition, potential mechanisms for redox signaling involved in mitochondrial remodeling and redox metabolism regulation are also reviewed.

This article focuses on the current underlying of molecular mechanisms of the peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) mediated pathway and discuss possible therapeutic benefits of increased mitochondrial biogenesis in compensating for mitochondrial dysfunction and ameliorating aging and aging-related diseases. PGC-1α is the master transcription regulator that stimulates mitochondrial biogenesis, by upregulating nuclear respiratory factors and mitochondrial transcription factor A, leading to increased mitochondrial DNA replication and gene transcription. PGC-1α also regulates cellular oxidant-antioxidant homeostasis by stimulating the gene expression of superoxide dismutase-2, catalase, glutathione peroxidase 1, and uncoupling protein. Recent reports from muscle-specific PGC-1α overexpression underline the benefit of PGC-1α in muscle atrophy and sarcopenia, during which PGC-1α enhanced mitochondrial biogenic pathway and reduced oxidative damage. Thus, PGC-1α seems to have a protective role against aging associated skeletal muscle deterioration.

The inflammatory response to exercise-induced muscle damage has been extensively described. Exercise has important modulatory effects on immune function. These effects are mediated by diverse factors including pro-inflammatory cytokines, classical stress hormones, and hemodynamic effects leading to cell redistribution. As has been reported regarding oxidative stress, inflammation can have both detrimental and beneficial effects in skeletal muscle. In this review we will address the role of inflammation on protein metabolism in skeletal muscle. Specifically, we will review studies showing that treatment with cyclooxygenase-inhibiting drugs modulate the protein synthesis response to one bout of resistance exercise and to training. Understanding how these drugs work is important for the millions of individuals worldwide that consume them regularly. We will also discuss the importance of reactive oxygen species and inflammatory cytokines in muscle adaptations to exercise and the Janus faced of the use of antioxidant and anti-inflammatory drugs by athletes for optimizing their performance, especially during the periods in which muscle hypertrophy is expected.

Interaction of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) with other cellular signalling pathways plays an important role in training-induced mitochondrial adaptations. The purpose of this study was to examine whether pyrolidine dithiocarbamate (PDTC), a nuclear factor-κB inhibitor and antioxidant, and the β-adrenergic blocker propranolol would affect the PGC-1α-induced mitochondrial transcription factors, enzymes and proteins involved in energy metabolism and antioxidant defense in response to endurance training. Female Sprague-Dawley rats (aged 8 weeks) were randomly divided into two groups (n = 24), one subjected to 8 weeks of treadmill training and one remaining sedentary. Each group of rats was subdivided in to three groups that were injected (i.p.) daily with PDTC (50 mg (kg body weight)(-1)), propranolol (30 mg kg(-1)) or saline as a control 1 h before the daily exercise session. Sedentary PDTC-treated rats showed 75% higher PGC-1α content (P < 0.01) but lower mitochondrial transcription factor A and phosphorylated cAMP-responsive element binding protein (p-CREB) than control rats. Training increased PGC-1α by 57% (P < 0.01), cytochrome c oxidase 4 by 30% (P < 0.05) and p-CREB by 13% (P < 0.05), whereas the mitochondrial mitofusin-2 level was decreased by 24% (P < 0.01). Treatment with PDTC decreased PGC-1α and p-CREB content by 34 and 53% (P < 0.05), respectively, in trained rats and abolished training effects on cytochrome c oxidase 4 and mitochondrial mitofusin-2. None of the training effects was abolished by propranolol treatment. Mitochondrial superoxide dismutase activity was decreased with PDTC, whereas training-induced glutathione peroxidase activity was unaltered by either drug. The data indicates that nuclear factor-κB-inhibitory and antioxidant properties of PDTC can attenuate PGC-1α-mediated mitochondrial adaptation to endurance training, whereas the β-adrenergic pathway has little adverse effect.

This paper reviews the current understanding of the molecular basis of the peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α)–mediated pathway and discusses the role of PGC-1α in skeletal muscle atrophy caused by immobilization. PGC-1α is the master transcription regulator that stimulates mitochondrial biogenesis, by upregulating nuclear respiratory factors (NRF-1, 2) and mitochondrial transcription factor A (Tfam), which leads to increased mitochondrial DNA replication and gene transcription. PGC-1α also regulates cellular oxidant–antioxidant homeostasis by stimulating the gene expression of superoxide dismutase-2 (SOD2), catalase, glutathione peroxidase 1 (GPx1), and uncoupling protein (UCP). Recent reports from muscle-specific PGC-1α overexpression underline the importance of PGC-1α in atrophied skeletal muscle, demonstrate enhancement of the PGC-1α mitochondrial biogenic pathway, and reduced oxidative damage. Thus, PGC-1α appears to play a protective role against atrophy-linked skeletal muscle deterioration.

In the present study, through a transmission experiment, the effects of europium complex and Eu3+ on the pearl colour in the pearl oyster Pinctada martensii were evaluated. Europium complex and europium salt were respectively enriched by dietary green algae platymonas subcordiformi, and their toxicity to algae were analysed by the 96-h acute toxic experiment. Then, the green algae enriched europium complex and europium salt were respectively fed pearl oysters for 2 months, and the surface microstructures of cultured pearls were presented with scanning electron microscopy (SEM) and atomic force microscope(AFM). The results show that toxicity of europium complex to algae is much lower than Eu3+ from lowest no observable effect concentration LNOEC values and 96h-EC50 values and two compounds can modify pearl structure and optimize pearl colour from SEM and AFM images. Taken together, our results, for the first time, show that rare earth complex can improve the pearl quality. This study provides an innovative approach for additional investigation of the influence of rare earth elements on pearls.

Avenanthramides (AVA), polyphenols found exclusively in oats ( Avena sativa L.), may play a role in the anti-inflammatory and antiatherogenic activity of oats. The bioavailability of AVA has been demonstrated previously, but its distribution at the organ and tissue level and the extent of conjugation following ingestion have been unexplored. Synthetic AVA was administered to 24 rats by oral gavage, whereas 6 control rats received saline. AVA concentrations were measured via HPLC in plasma, liver, heart, and gastrocnemius (GAS) obtained over a 12 h period (0, 2, 4, 12 h; n = 6 at each time point). Samples were extracted with and without glucuronidase-sulfatase to assess the level of conjugation. We conclude that AVA are bioavailable to the blood circulation following oral ingestion in the rat and reach peripheral tissues where they can be taken up by various organs differentially. With AVA remaining in the organs for up to 12 h, it seems possible to maintain an increased level of AVA in the rat via repeated feedings.

Ferulic acid ethyl ester (FAEE) and ferulic acid (FA) were fed to rats to determine in vivo efficacy in elevating selected phase II enzyme activities and antioxidant capacity. Male Sprague–Dawley rats were fed the AIN-93M control diet, or the control diet supplemented with 1% FA, 1% FAEE, or 0.1% FAEE for 2 weeks. Quinone reductase (QR), glutathione-S-transferase (GST), thioredoxin reductase (TxR) activities, and oxidised and reduced glutathione were determined for brain, lung, liver, kidney, intestine and colon tissues. Both FA and FAEE (1%) supplementation increased QR and GST specific activities in kidney and colon tissues by 23–38% relative to the control diet. FAEE (1%) supplementation also induced QR specific activity, by 1.46- and 1.27-fold over the control diet, in intestinal and lung tissue of animals, whereas FA did not. No effect of diet was observed on liver cytochrome P450-1A1 activity. These results demonstrate that dietary FA and FAEE induce QR activity in the colon, small intestine, lung, and kidney, and improve glutathione antioxidant status in the colon and intestine. Therefore, dietary FA and FAEE may elevate defences to oxidative- and xenobiotic-induced stress in vivo.

Neural stem cells (NSCs) are multipotent stem cells that have the potential to differentiate into different cells of the neural lineage like neurons, astrocytes and oligodendrocytes. In the current work, we explored whether NSCs could be differentiated into functional Schwann-like cells, which has not been investigated up to date. NSCs were harvested from the hippocampus of rats and identified by single cell cloning and immunofluorescence staining. Then NSCs were treated with DMEM/F12 supplemented with forskolin, heregulin, bFGF, PDGF-AA and retinoic acid (RA). Differentiated NSCs (dNSCs) exhibited a spindle-like morphology similar to Schwann cells and expressed the glial markers p75 and S100. We also found that dNSCs could enhance neurite outgrowth when co-cultured with NG108-15 cells. These results indicated that NSCs, derived from hippocampus of rats, could differentiate into Schwann-like cells with morphological, phenotypic and functional similarities.

Exercise induced adaptations in muscle are highly specific and dependent upon the type of exercise, as well as its frequency, intensity, and duration. Mitochondria are highly dynamic organelles. Fusion and fission reactions lead to a continuous remodeling of the mitochondrial network, which range from reticulum of elongated and branched filaments to collections of individual organelles. Mitochondrial network dynamics are sensitive to various physiological and pathological stimuli, and mitochondrial morphological changes are no epiphenomena, but central to cell function and survival. There is a strong correlation between mitochondrial network morphology, dynamic-related protein, and energy metabolism. It is expected that alteration in cellular energy status during exercise can also be achieved through mitochondrial network dynamics. In this review, we describe mitochondrial network remodeling response to acute and endurance exercise, which is accompanied by bioenergetics and redox regulation. In addition, potential mechanisms for metabolic and redox signaling involved in mitochondrial dynamic regulation are also reviewed.

Eccentric contraction (EC) is known to elicit inflammation and damage in skeletal muscle. Proinflammatory cytokine TNF-α plays an important role in this pathogenesis, but the time course of its response to EC and the regulatory mechanisms involved are not clear. The purpose of the study is twofold: 1) to investigate the gene expression of TNF-α in rat muscle during and after an acute bout of downhill running and the associated oxidoreductive (redox) changes; and 2) to examine whether EC activates muscle ubiquitin-proteolytic pathway resulting in necrosis and oxidative damage. Female Sprague-Dawley rats (age 3 mo) were randomly divided into five groups ( n = 6) that ran on treadmill at 25 m/min at −10% grade for 1 h ( group 1) or 2 h ( group 2) and were killed immediately; ran for 2 h and killed at 6 h after exercise ( group 3), ran for 2 h and killed at 24 h after exercise ( group 4); and killed at rest as controls ( group 5). TNF-α mRNA and protein content showed progressive increases in the deep portion of vastus lateralis (DVL) and gastrocnemius muscles during and after EC. These changes were accompanied by a progressive decrease of mitochondrial aconitase activity and NF-κB activation. After 2 h of exercise, elevated levels of serum TNF-α, endotoxin, creatine kinase, and lipid peroxidation marker were evident and persisted through 24 h postexercise. At 24 h, there were marked increases in H2O2concentration, myleoperoxidase activity, and endotoxin level, along with nuclear accumulation of p65, in both muscles. mRNA level of ubiquitin-conjugating enzymes (E2)-14k was progressively upregulated during exercise and recovery, whereas the expression of the Toll-like receptor 4 (TLR4) in DVL was downregulated in both muscles. We conclude that prolonged EC induces TNF-α expression possibly due to NF-κB activation stimulated by increased reactive oxygen species generation and endotoxin release. These inflammatory and prooxidative responses may underlie the processes of muscle proteolysis and oxidative damage.

The purpose of this study was to investigate the changes in the gene expression of Mitofusion (Mfn) 1 and 2 and Fission 1 (Fis1) and mitochondrial energy metabolism in response to altered energy demand during prolonged exercise in rat skeletal muscle. Male Sprague-Dawley rats were subjected to an acute bout of treadmill running at various durations and killed immediately or during recovery. Mfn1/2 and Fis1 mRNA and protein contents, reactive oxygen species (ROS) generation, state 3 and state 4 respiration rates, trans-innermembrane potential and ATP synthase activity were measured in isolated muscle mitochondria. We found that (1) Mfn1/2 mRNA contents were progressively decreased during 150 min of exercise, along with decreased Mfn 1 protein levels. Fis1 mRNA and protein contents showed significant increases after 120-150 min of exercise. These changes persisted through the recovery period up to 24 h. (2) Mitochondrial ROS generation and state 4 respiration showed progressive increases up to 120 min, but dropped at 150 min of exercise. (3) State 3 respiration rate and respiratory control index were unchanged initially but decreased at 150 and 120 min of exercise, respectively, whereas ATP synthase activity was elevated at 45 min and returned to resting level thereafter. Our data suggested that the gene expression of mitochondrial fusion and fission proteins in skeletal muscle can respond rapidly to increased metabolic demand during prolonged exercise, which could significantly affect the efficiency of oxidative phosphorylation.

Skeletal muscle contraction, growth, differentiation and adaptation are governed by complicated biological mechanisms still being studied intensively. Generation of reactive oxygen and nitrogen species (RS) is one of the most prominent events during contractile activity that could influence muscle function and health. While RS generation is known to cause oxidative stress, activate certain pathogenic pathways and aging, they also serve as useful signaling molecules to regulate gene expression of proteins and enzymes that play a vital role in the normal muscle function and defense against detrimental effects of RS. The purpose of the present review is two-fold: first, to provide an overview of cell signaling controlled by a redox sensitive mechanism and its impact on skeletal muscle health and function; and second, to review the various muscular diseases and disorders that have an etiological origin of RS overproduction and/or inadequate antioxidant defense. Given the physiological role of skeletal muscle we will emphasize the importance of physical exercise in promoting cellular antioxidant defense and its benefits in the maintenance of muscle health.

Andrographolide (ANDRO), a diterpenoid lactone isolated from the traditional herbal plant Andrographis paniculata, was reported to induce apoptosis in hepatoma Hep3B cells in our previous study (Ji LL, Liu TY, Liu J, Chen Y, Wang ZT. Andrographolide inhibits human hepatoma-derived Hep3B cells growth through the activation of c-Jun N-terminal kinase. Planta Med 2007; 73: 1397-1401). The present investigation was carried out to observe whether cellular reduced glutathione (GSH) plays important roles in ANDRO-induced apoptosis. ANDRO initially increased intracellular GSH levels which then decreased later, while inhibition of cellular GSH synthesis by L-Buthionine-(S,R)-sulfoximine (BSO) augmented ANDRO-induced cytotoxicity and apoptosis in Hep3B cells. On the other hand, the thiol antioxidant dithiothreitol (DTT) rescued ANDRO-depleted cellular GSH, and abrogated ANDRO-induced cytotoxicity and apoptosis. Furthermore, BSO pretreatment augmented ANDRO-decreased expression of antioxidant protein thioredoxin 1 (Trx1), while DTT reversed this decrease. Further results showed that ANDRO increased the activity of the GSH-related antioxidant enzyme glutathione peroxidase (GPx) and the production of intracellular reactive oxygen species (ROS). Taken together, this study demonstrates that the intracellular redox system plays important roles in regulating the cytotoxicity of ANDRO on hepatoma Hep3B cells.

To determine whether American ginseng (Panax Quinquefolium) confers antioxidant protection to postmenopausal women at rest and after a mild aerobic exercise session.In this double-blinded parallel study, 12 female subjects (age range 55-75) consumed two capsules, containing 500 mg of dry American ginseng whole-root powder, everyday for 4 months, whereas 13 female control subjects of the same age range consumed two placebo capsules. Before and after the supplementation regimen each subject performed 30 minutes of treadmill walking on a 5% grade incline at an estimated 60% of VO(2)max.Ginseng supplementation had no effect on heart rate, blood pressure, plasma blood glucose, or lactate concentration at rest or immediately after exercise tests. The ginseng supplemented group displayed a higher resting plasma glutathione disulfide (GSSG) concentration and lower glutathione (GSH):GSSG ratio, as well as a lower resting total antioxidant content (TAC). Plasma GSSG concentration decreased, whereas the GSH:GSSG ratio and TAC increased after exercise in all subjects. Furthermore, plasma malondialdehyde and urine 8-hydroxydeoxyguanosine concentrations were elevated in the ginseng-supplemented group. Erythrocyte superoxide dismutase and GSH reductase activities were increased after ginseng supplementation. The 30-minute treadmill walking, however, did not alter these changes.These data suggest that chronic American ginseng supplementation at the given dose can cause an oxidative stress in postmenopausal women, as reflected by the elevated oxidative damage markers and the increased erythrocyte antioxidant enzyme activity.

Contraction-induced production of reactive oxygen and nitrogen species has been shown to cause oxidative stress to skeletal muscle, heart and other organs. As an adaptive response, muscle antioxidant defense systems are upregulated in response to exercise to restore intracellular prooxidant- antioxidant homeostasis. Thus, both young and old animals and humans involved in regular exercise have shown reduced oxidative damage during acute physical exertion at accustomed or excessive intensity, or under oxidative challenges otherwise deemed detrimental. The current article provides a brief review of this exercise-induced hormesis with the emphasis on the role of redox sensitive signal transduction pathways (mainly nuclear factor κB and mitogen-activated protein kinase) that can activate the gene expression of antioxidant enzymes and proteins. Molecular mechanisms and gene targets for these signaling pathways, as well as the biological significance of the adaptations, are discussed.

Neoandrographolide, one of the principal diterpene lactones, isolated from a medicinal herb Andrographis paniculata Nees, was tested in vivo and in vitro for its anti-inflammatory activities and mechanism. Oral administration of neoandrographolide (150 mg/kg) significantly suppressed ear edema induced by dimethyl benzene in mice. Oral administration of neoandrographolide (100–150 mg/kg) also reduced the increase in vascular permeability induced by acetic acid in mice. In vitro studies were performed using the macrophage cell line RAW264.7 to study the effect of neoandrographolide on suppressing phorbol-12-myristate-13-acetate (PMA)-stimulated respiratory bursts and lipopolysaccharide (LPS)-induced production of nitric oxide (NO) and tumor necrosis factor-alpha (TNF-α). Respiratory bursts were quantified by chemiluminescence (CL) measurements.Results showed that neoandrographolide suppressed PMA-stimulated respiratory bursts dose-dependently from 30 μM to 150 μM. Neoandrographolide also inhibited NO and TNF-α production in LPS-induced macrophages, contributing to the anti-inflammatory activity of A. paniculata. These results indicate that neoandrographolide possesses significant anti-inflammatory effects, which implies that it would be one of the major contributing components to participate in the anti-inflammatory effect of A. paniculata. and a potential candidate for further clinical trial.

Loss of mitochondrial structural and functional integrity plays a critical role in the pathogenesis of muscle disuse atrophy. Peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α) has been suggested to modulate autophagy-lysosome pathway (mitophagy) during muscle atrophy, but clear evidence is still lacking. In the current study, we tested the hypothesis that overexpression of PGC-1α via in vivo transfection would ameliorate mitophagy in mouse tibialis anterior muscle subjected to two weeks of immobilization (IM), followed by remobilization (RM). While mitochondrial biogenesis and antioxidant enzymes are decreased, all autophagic and mitophagic protein markers such as Beclin-1, Bnip3, PINK1, parkin, Mul1 and the LC3II/LC3I ratio were increased in IM-RM muscle together with activation of FoxO pathway. Overexpression of PGC-1α significantly increased mitochondrial DNA proliferation and oxidative enzyme activity, whereas it mitigated oxidative stress and mitochondrial ubiquination in IM-RM muscle. Protein contents of PINK1, parkin and Mul1 in mitochondria decreased by approximately 50% with PGC-1α treatment. Furthermore, PGC-1α overexpression suppressed FoxO1 and FoxO3 activation along with a decreased LC3II/LC3I ratio. Importantly, PGC-1α attenuated IM-RM-induced ubiquination and degradation of mitofusion protein Mfn2. Muscle apoptotic tendency, measured by Bax/Bcl2 ratio and caspase-3 activity, were elevated with IM-RM, but unaffected by PGC-1α. We conclude that overexpression of PGC-1α by in vivo transfection can inhibit activation of mitophagy pathway in the atrophying muscle caused by immobilization.

Activated macrophages express inducible isoforms of nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), produce excessive amounts of nitric oxide (NO) and prostaglandin E(2) (PGE(2)), which play key roles in the processes of inflammation. Andrographis paniculata Nees is a traditional Chinese herb commonly used for treatment of infection, inflammation, and diarrhea. However, the mechanism of its therapeutic function is not well known. In the present study, the effect of neoandrographolide, one of bioactive components in A. paniculata, on iNOS-mediated NO production and COX-2-mediated PGE(2) in bacterial lipopolysaccharide (LPS) stimulated-murine macrophages was investigated. Neoandrographolide at concentrations (30-90 microM) significantly (p0.05) inhibited the productions of NO and PGE(2) in LPS stimulated macrophages without inducing cytotoxicity. The effect of neoandrographolide also has been investigated on iNOS and COX-2 expression in activated macrophage by using RT-PCR and immunoblotting. The inhibition of NO release by neoandrographolide can be attributed to the block of iNOS mRNA transcription followed by inhibiting protein expression. However, neoandrographolide inhibited COX-2 protein expression only but without inhibiting COX-2 mRNA expression, which was involved in the inhibitory activity against the PGE(2 )overproduction. This suggests that the effect of neoandrographolide on iNOS expression may occur at the transcriptional level and the inhibition of COX-2 expression occurs at the translational level. Furthermore, we have found that the addition of neoandrographolide inhibited the activation of p38 mitogen-activated protein kinase (MAPKs) instead of JNK, ERK1/2, or NF-kappaB. These results indicated that the anti-inflammatory properties of neoandrographolide might result from the inhibition of iNOS and COX-2 expression through inhibiting p38 MAPKs activation. Therefore, neoandrographolide isolated from A. paniculata could be offered as a leading compound for anti-inflammation.

Aims. – To assess the role of the reactive oxygen species (ROS) in cell signalling and in the regulation of gene expression. Methods. – Exercise causes oxidative stress only when exhaustive. Strenuous exercise causes oxidation of glutathione, release of cytosolic enzymes, and other signs of cell damage. We have tested this hypothesis by studying the effect of inhibition of ROS production by allopurinol (an inhibitor of xanthine oxidase, a free radical generating enzyme) on cell signalling pathways in marathon runners and in rats submitted to exhaustive exercise by running on a treadmill. Results. – Exercise caused an activation of NF-κB in lymphocytes from marathon runners which was completely prevented by allopurinol. In the rat model exercise caused an activation of MAP kinases in gastrocnemius muscle. This in turn activated the NF-κB pathway and consequently the expression of important enzymes associated with defence against ROS (superoxide dismutase) and adaptation to exercise (eNOS and iNOS). All these changes were abolished when ROS production was prevented by allopurinol. Conclusion. – Thus we report evidence that ROS act as signals in exercise because decreasing their formation prevents activation of important signalling pathways which cause useful adaptations in cells. Because these signals result in an up-regulation of powerful antioxidant enzymes, exercise itself can be considered as an antioxidant.

Reactive oxygen or nitrogen species (RONS) are produced during exercise due, at least in part, to the activation of xanthine oxidase. When exercise is exhaustive they cause tissue damage; however, they may also act as signals inducing specific cellular adaptations to exercise. We have tested this hypothesis by studying the effects of allopurinol-induced inhibition of RONS production on cell signalling pathways in rats submitted to exhaustive exercise. Exercise caused an activation of mitogen-activated protein kinases (MAPKs: p38, ERK 1 and ERK 2), which in turn activated nuclear factor κB (NF-κB) in rat gastrocnemius muscle. This up-regulated the expression of important enzymes associated with cell defence (superoxide dismutase) and adaptation to exercise (eNOS and iNOS). All these changes were abolished when RONS production was prevented by allopurinol. Thus we report, for the first time, evidence that decreasing RONS formation prevents activation of important signalling pathways, predominantly the MAPK–NF-κB pathway; consequently the practice of taking antioxidants before exercise may have to be re-evaluated.

Clivorine, a pyrrolizidine alkaloid, is a potent toxic compound extracted from a Chinese medicinal plant Ligularia hodgsonii Hook. We have previously shown that clivorine inhibited human normal liver L-02 cells proliferation and induced p38 mitogen-activated protein kinase phosphorylation. The aim of this study is to further observe the mechanism of clivorine-inhibited L-02 cells growth. In this paper we show here that clivorine can induce apoptosis in L-02 cells, reduce the expression of p53 protein but has no effect on the expression of Bcl-2 protein, and clivorine also induces the cleavage of the poly(ADP-ribose) polymerase in L-02 cells. Our results suggest that the anti-proliferative function of clivorine in L-02 cells may be due to its inducing cell apoptosis, and clivorine-induced cell apoptosis is independent of p53 protein.

Phytochemicals are emerging comprehensive and versatile sources of antioxidants to be consumed to enhance the body's defenses against harmful reactive oxygen species generated endogenously or exogenously. Tocols, favonoids, and phenolic acids compose the majority of this class of antioxidants, although more complex compounds may also be involved, such as ginsenosides. In vitro and in vivo studies have demonstrated convincingly that dietary supplementation of phytochemicals has beneficial effects against certain types of pathogenesis, disease, cancer, and aging. There is evidence that these effects are related to the ability of phytochemicals to promote the antioxidant defense system and reduce oxidative stress and damage in the cell. However, due to their structural and chemical diversity and complexity, many of the benefits as well as potential adverse effects remain to be examined.

Avenanthramides (AVEN) are major phenolic acids in oat (Avena sativa L.) that have potent antioxidant functions. Female Sprague-Dawley rats (n = 48, age 6-7 wk) were fed either an AIN-93 based control (C) diet or the same diet containing 0.1 g/kg AVEN-Bc [N-(3′,4′-dihydroxycinnamoyl)-5-hydroxyanthranilic acid] for 50 days. Each group was further divided into rested (R) and exercised (E, treadmill running at 22.5 m/min, 10% grade for 1 hour) prior to killing. AVEN supplementation per se had no effect on reactive oxygen species (ROS) production in most tissues, except soleus muscle wherein ROS level was decreased. AVEN-fed rats had higher superoxide dismutase (SOD) activity in the deep portion of vastus lateralis muscle (DVL), liver and kidney and higher glutathione peroxidase (GPX) activity in the heart and DVL, compared to C-fed rats. E increased ROS production in the liver, DVL and soleus, and lipid peroxidation in the heart, liver and DVL. AVEN attenuated E-induced ROS in soleus and lipid peroxidation in the heart, but enhanced lipid peroxidation in DVL. We conclude that AVEN can serve as a potential dietary antioxidant supplement, but its tissue specific effects require further investigation.

The effects of endurance training and acute exhaustive exercise on plasma levels of three superoxidedismutase (SOD) isoenzymes and the ability of superoxide generation in neutrophils were studied. Eighteen healthy male students, aged 17-22 years, who volunteered for this study, underwent three months of endurance training in swimming or running. Before and after the training course, they performed acute exercise and blood samples were collected before and after this exercise. The endurance training significantly increased maximal oxygen uptake (VO2max) in all subjects. Neither the endurance training nor the acute exercise affected the plasma CuZn-SOD level. Acute exercise after the training, but not before the training, increased both the plasma Mn-SOD and extracellular SOD (EC-SOD) levels by 33.6 and 33.5%, respectively. The training decreased the EC-SOD level at rest by 22.2%. Acute exercise after the training, but not before the training, increased the plasma lipid peroxide level, suggesting higher oxidative stress in trained subjects during exhaustive exercise. The ability of neutrophils to generate superoxide was increased by the acute exercise, but induction of the superoxide was suppressed after training. These results indicate that EC-SOD levels were changed in a different manner from the CuZn-SOD and Mn-SOD: it was decreased by training but was increased by acute exercise, suggesting that endurance training increases the reserve of EC-SOD in tissues. The results also suggest the possibility of plasma EC-SOD assay as a new index of endurance training.

Clivorine, a pyrrolizidine alkaloid extracted from Chinese medicinal plant Ligularia hodgsonii Hook significantly inhibited human normal liver L-02 cells proliferation and decreased L-02 cells viability. The results of western blot showed that clivorine strongly evoked phosphorylation of p38 mitogen-activated protein (MAP) Kinase in L-02 cells, but had no effect on extracellular signal-related kinases MAP Kinase phosphorylation. Moreover, another pyrrolizidine alkaloid monocrotaline had no effect on phosphorylation of p38 MAP Kinase in L-02 cells. These studies document the effects of pyrrolizidine alkaloid clivorine on the MAPK cascade and on the growth of human normal liver L-02 cells for the first time, which may be a possible reason for the toxic effects observed in those plants containing pyrrolizidine alkaloids.

Maintaining mobility is a critical element for the quality of life. Skeletal muscle, the primary organ for locomotion, undergoes age-associated deterioration in size, structure, and function. Recent research suggests that oxidative stress is an important etiology for sarcopenia. The level of oxidative stress imposed on aging muscle is influenced by two fundamental biological processes: the increased generation of reactive oxygen species (ROS) and age-associated changes in antioxidant defense. It appears that despite increased ROS production, aging muscle has a decreased gene expression of antioxidant enzymes possibly due to a diminished ability for cell signaling. A major benefit of nonexhaustive exercise is to induce a mild oxidative stress that stimulates the expression of certain antioxidant enzymes. This is mediated by the activation of redox-sensitive signaling pathways. For example, gene expression of muscle mitochondrial (Mn) superoxide dismutase is enhanced after an acute bout of exercise preceded by an elevated level of NF-kappaB and AP-1 binding. An increase in de novo protein synthesis of an antioxidant enzyme usually requires repeated bouts of exercise. Aging does not abolish but seems to attenuate training adaptations of antioxidant enzymes. Thus, for senescent muscle, training should be assisted with supplementation of exogenous antioxidants to research the optimal level of defense.

Prolonged immobilization (IM) causes skeletal muscle atrophy characterized by mitochondrial deterioration and proteolysis. Muscle remobilization (RM) increases reactive oxygen species generation, proinflammatory cytokine expression, and oxidative stress, preventing muscle from quick recovery. Thus, we hypothesized that overexpression of peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α) via in vivo transfection would promote mitochondrial biogenesis and antioxidant defense, thus ameliorating the aforementioned deteriorations in a mouse model with 14-d IM followed by 5-d RM. PGC-1α transfection in tibialis anterior muscle resulted in a 7.2- and 4-fold increase in PGC-1α content in cytosol and nucleus, respectively. Mitochondrial biogenic (cytochrome c, mitochondrial transcription factor A), morphologic (mitochondrial density, mDNA/nDNA ratio), and functional (cytochrome c oxidase activity, ATP synthesis rate) markers, as well as fiber cross-sectional area, significantly increased in IM-RM muscle by PGC-1α overexpression. These effects were accompanied by an 18% decrease in H2O2, 30% decrease in nuclear factor-κB-DNA binding, and 25% reduction of IL-1β and-6 production in IM-RM muscle. There was a 34% increase in superoxide dismutase-2 activity, along with a 3.5-fold increase in NAD-dependent deacetylase sirtuin-3 expression caused by enhanced PGC-1α-estrogen-related receptor α binding. Our findings highlighted the importance of PGC-1α in protecting muscle from metabolic and redox disturbances caused by IM.—Kang, C., Goodman, C. A., Horberger, T. A., Ji, L. L. PGC-1α overexpression by in vivo transfection attenuates mitochondrial deterioration of skeletal muscle caused by immobilization.

An acute bout of prolonged exercise has been shown to decrease hepatic fatty acid synthase (FAS) mRNA and activity induced by high carbohydrate diets. The purpose of the current study was to examine the role of insulin in this exercise down-regulation of FAS. Sixty-four male Wistar rats were randomly divided into normal and streptozotocin (STZ)-treated diabetic groups. After being starved for 48 h and refed a high cornstarch (C) or fructose (F) diet for 10 h, one half of each group of rats was killed after an acute bout of prolonged exercise (E), while the other half of the group was killed in the rested state. STZ treatment suppressed plasma insulin and elevated plasma glucagon levels along with a severe hyperglycemia. FAS mRNA levels decreased by 60% (P < 0.05) with STZ treatment but were 250% higher in F-fed versus C-fed rats. E abolished F-induced FAS mRNA levels in both normal and STZ rats and decreased plasma glucose concentration in STZ rats (P < 0.05). F-fed normal rats showed twofold higher hepatic FAS activity than did C-fed normal rats and this dietary induction was abolished by STZ (P < 0.05). FAS activity in normal rats was not affect by E and was increased with E in STZ rats. Nuclear protein binding to the insulin response sequence was not affected by STZ or diet and increased with E (P < 0.05). Carbohydrate response element binding was greater with F- versus C-feeding (P < 0.05) but unaffected by E. E enhanced inverted CCAAT-box element binding regardless of diet and STZ. We conclude that although insulin status had a great influence on FAS gene expression, E-induced down-regulation of FAS mRNA was not mediated by altered insulin response sequence binding but primarily by increased inverted CCAAT-box element binding to the FAS promoter and/or decreased concentration of carbohydrate metabolites.