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Exercise and healthy diet consumption support healthy aging. Schisandra chinensis (Turcz.) also known as "Baill." has anti-inflammatory and antioxidant properties. However, the role of S. chinensis as an antiaging compound has yet to be demonstrated. This study elucidated the antiaging effect of S. chinensis ethanol-hexane extract (C1) and the effect of C1 treatment on muscle and bone following physical exercise in ovariectomized (OVX) rats. RAW 264.7, human diploid fibroblasts (HDFs), C2C12 myoblasts, bone marrow macrophages, and MC3T3-E1 cells were used for in vitro, and muscle and bone of OVX rats were used for in vivo study to demonstrate the effect of C1. The C1 significantly inhibited the expression of inflammatory molecules, β-galactosidase activity, and improved antioxidant activity via down-regulation of reactive oxygen species in RAW 264.7 and aged HDF cells. The C1 with exercise improved muscle regeneration in skeletal muscle of OVX rats by promoting mitochondrial biogenesis and autophagy. C1 induced osteoblast differentiation, and C1 + exercise modulated the bone formation and bone resorption in OVX rats. C1 exhibited anti-inflammatory, antioxidant, myogenic, and osteogenic effects. C1 with exercise improved age-related muscle wasting and bone loss. Therefore, S. chinensis may be a potential prevent agent for age-related diseases such as sarcopenia and osteoporosis. [ABSTRACT FROM AUTHOR]

New Findings: What is the central question of this study?What is the effect and mechanism of interval running training on age‐related muscle wasting and bone loss in an ovariectomized rat model?What is the main finding and its importance?Interval running training improved muscle growth and osteogenic differentiation by enhancing the expression of bone morphogenic proteins and sirtuins in ageing‐induced ovariectomized rats. Therefore, the repetition of low and high intensities within a single exercise bout, such as interval running training, may be recommended as a practical intervention to prevent skeletal muscle wasting and bone loss in the elderly. Effective prophylactic strategies are needed for the suppression of age‐related muscle wasting and bone loss after menopause. Exercise training is attractive due to its potential for improving energy metabolism, as well as age‐related muscle wasting and bone loss. In particular, interval running (IR) training involves a repetition of low and high intensities within a single exercise bout. Therefore, this study elucidated the effect of interval training on muscle and bone health, as well as anti‐ageing, in ovariectomized (OVX) rats. The anti‐ageing effect of IR on muscle and bone was tested using western blotting and micro‐computed tomography analysis, tartrate‐resistant acid phosphatase and immunohistochemical staining. IR significantly inhibited the expression of inflammatory molecules, and improved antioxidant activity via down‐regulation of mitogen‐activated protein kinases (MAPKs) in the ageing‐induced OVX rats skeletal muscle. IR compared with continuous running (CR) improved muscle mass and growth in OVX rats by the promotion of muscle growth‐related factors including MyoD, myogenin, phospho‐mechanistic target of rapamycin (p‐mTOR), sirtuins (SIRTs), and bone morphogenic proteins (BMPs). IR also effectively recovered OVX‐induced bone loss via the down‐regulation of bone resorption and osteoclast formation in receptor activator of nuclear factor κB ligand (RANKL)‐treated bone marrowmacrophages (BMMs). In particular, IR led to high expression of SIRT1 and 6, which promoted osteogenic differentiation and bone formation via modulating the BMP signalling pathway compared with CR training. The in vivo effect of IR was confirmed by immunohistochemical staining with the improvement of bone formation molecules such as BMPs and SIRTs. These results suggested that IR training affected myogenic and osteogenic formation. So, IR training may be considered for prevention of muscle wasting and bone loss for the elderly. [ABSTRACT FROM AUTHOR]

Gomisin A from the fruit of Schisandra chinensis has many pharmacological properties, including hepato-protective, anti-diabetic, and anti-oxidative stress. However, the potential benefit of gomisin A is still not well understood, especially in aging progression. Therefore, the aim of this study was to clarify whether the promotion of mitochondrial biogenesis and autophagy of gomisin A affects anti-aging progression, and its mechanism. Intermediate (PD32) human diploid fibroblast (HDF) cells were brought to stress-induced premature senescence (SIPS) using hydrogen peroxide. Gomisin A inhibited reactive oxygen species production even in the SIPS-HDF cells. Gomisin A was also able to attenuate the activity of senescence-associated ß-galactosidase and the production of pro-inflammatory molecules in the SIPS as well as aged HDF cells. The antioxidant activity of gomisin A was determined by recovering the Cu/Zn, Mn-SOD, and HO-1 expression in the SIPS-HDF cells. In mechanistic aspect, gomisin A inhibited the mitogen-activated protein kinase pathway and the translocation of nuclear factor kappa B to the nucleus. In addition, gomisin A promoted the autophagy and mitochondrial biogenesis factors through the translocation of nuclear factor erythroid 2-related factor-2, and inhibited aging progression in the SIPS-HDF cells. In summary, the enhanced properties of mitochondrial biogenesis and autophagy of gomisin A has a benefit to control age-related molecules against SIPS-induced chronic oxidative stress, and gomisin A may be a potential therapeutic compound for the enhancement of intracellular homeostasis to aging progression. [ABSTRACT FROM AUTHOR]

New Findings What is the central question of this study? Exercise training by running has an effect on age-related muscle and bone wasting that improves physical activity and quality of life in the elderly. However, the effect of downhill running on age-related muscle and bone wasting, and its mechanisms, are unclear., What is the main finding and its importance? Gradual downhill running can improve skeletal muscle growth and bone formation by enhancing autophagy and bone morphogenetic protein signalling in aged rats. Therefore, downhill running exercise might be a practical intervention to improve skeletal muscle and bone protection in the elderly., Recent evidence suggests that autophagy and the bone morphogenetic protein (BMP) signalling pathway regulate skeletal muscle growth and bone formation in aged rats. However, the effect of downhill running on muscle growth and bone formation is not well understood. Thus, we investigated the effect of downhill and uphill running on age-related muscle and bone weakness. Young and late middle-aged rats were randomly assigned to control groups (young, YC; and late middle-aged, LMC) and two types of running training groups (late middle-aged downhill, LMD; and late middle-aged uphill, LMU). Training was progressively carried out on a treadmill at a speed of 21 m min−1 with a slope of +10 deg for uphill training versus 16 m min−1 with a slope of −16 deg for downhill training, both for 60 min day−1, 5 days week−1 for 8 weeks. Downhill and uphill training increased autophagy-related protein 5, microtubule-associated protein light chain, Beclin-1 and p62 proteins in aged rats. In addition, superoxide dismutase, haem oxygenase-1 and the BMP signalling pathway were elevated. Phosphorylation of mammalian target of rapamycin and myogenic differentiation were increased significantly in the LMD and LMU groups. Consequently, in the femur, BMP-2, BMP-7 and autophagy molecules were highly expressed in the LMD and LMU groups. These results suggest that both downhill and uphill training appear to have a positive effect on expression of autophagy molecules and BMPs. In particular, these physiological adaptations from gradual downhill exercise have an effect on bone morphological changes and muscle quality similar to gradual uphill training interventions in ageing. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine the pattern of the antibacterial activity of chlorhexidine digluconate ( CHX) against mature Streptococcus mutans biofilms. Streptococcus mutans biofilms were formed on saliva-coated hydroxyapatite discs and then treated with 0-20% CHX, once, three times, or five times (1 min per treatment) during the period of mature biofilm formation (beyond 46 h). After the treatments, the colony-forming unit ( CFU) counts of the treated biofilms were determined. The pH values of the spent culture medium were also determined to investigate the change in pH resulting from the antibacterial activity of CHX. The relationships between the concentration of CHX and the CFU counts and the concentration of CHX and culture medium pH, relative to the number of treatments performed, were evaluated using a sigmoidal curve-fitting procedure. The changes in CFU counts and culture medium pH followed sigmoidal curves and were dependent on the concentration of CHX ( R2 = 0.99). The sigmoidal curves were left-shifted with increasing number of treatments. Furthermore, the culture-medium pH of the treated biofilms increased as their CFU counts decreased. The lowest CHX concentration to increase culture-medium pH above the critical pH also decreased as the number of treatments increased. These results may provide fundamental information for selecting the appropriate CHX concentrations to treat S. mutans biofilms. [ABSTRACT FROM AUTHOR]

This study investigated whether multiple bioactivity of terrein such as anti-inflammatory and anti-oxidant inhibits age-related inflammation by promoting an antioxidant response in aged human diploid fibroblast (HDF) cells. HDF cells were cultured serially for in vitro replicative senescence. To create the ageing cell phenotype, intermediate stage (PD31) HDF cells were brought to stress-induced premature senescence (SIPS) using hydrogen peroxide (H2O2). Terrein increased cell viability even with H2O2 stress and reduced inflammatory molecules such as intracellular adhesion molecule-1 (ICAM-1), cyclooxygenase-2 (COX-2), interleukin-1beta (IL-1β) and tumour necrosis factor-alpha (TNF-α). Terrein reduced also phospho-extracellular kinase receptor1/2 (p-EKR1/2) signalling in aged HDF cells. SIPS cells were attenuated for age-related biological markers including reactive oxygen species (ROS), senescence associated beta-galactosidase (SA β-gal.) and the aforementioned inflammatory molecules. Terrein induced the induction of anti-oxidant molecules, copper/zinc-superoxide defence (Cu/ZnSOD), manganese superoxide dismutase (MnSOD) and heme oxygenase-1 (HO-1) in SIPS cells. Terrein also alleviated reactive oxygen species formation through the Nrf2/HO-1/p-ERK1/2 pathway in aged cells. The results indicate that terrein has an alleviative function of age-related inflammation characterized as an anti-oxidant. Terrein might be a useful nutraceutical compound for anti-ageing. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Peroxisome proliferator activated receptor gamma (PPARγ) has been known for their anti-inflammatory effects. But the application of this molecule in implant-induced inflammation has not been clearly studied yet. Here, we determined in vivo anti-inflammatory and osteogenic effects of PPARγ coated dental implant in the rat mandible. We used chitosan gold nanoparticles (Ch-GNPs) as a non viral vector to carry PPARγ plasmid DNA. Ch-GNPs were conjugated with PPARγ plasmid DNA through a coacervation process. Conjugation was cast over titanium (Ti) implants (4.5 × 0.8 mm) by dipping, and implants were installed in rat mandibles. One, 2, 3, and 6 weeks post-implantation, mandibles were examined by microcomputed tomography (µCT), immunohistochemistry, hematoxylin & eosin, and tartrate resistance acid phosphatase (TRAP) staining. In vivo Ch-GNPs/PPARγcoated implants were associated with inhibition of implant induced inflammatory molecules interleukin-1β and receptor activator of nuclear factor kappa-B ligand and enhanced expression of osteogenic molecules like bone morphogenetic protein 2 and 7 (BMP-2/-7) by up-regulating anti-oxidant molecules heme oxygenase-1. µCT demonstrated that PPARγ overexpression increased the density and volume of newly formed bone surrounding the implants compared to control ( n = 4; p < 0.05). Also, PPARγ reduced the number of TRAP positive cells. These results support the view that PPARγ overexpression diminishes inflammation and enhances osteogenesis around the dental implants. Thus, implant coated with anti-inflammatory molecules could have a significant utilization for the preparation of new biomaterials and may serve as prosthetic materials in patients suffering from inflammatory bone disease. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 103B: 587-595, 2015. [ABSTRACT FROM AUTHOR]

Objectives To deliver the efficacy and safety of Ch- GNPs (Chitosan gold nanoparticles) conjugated anti-inflammatory molecules peroxisome proliferator activated receptor gamma ( PPARγ) on implant surface titanium (Ti) to reduce implant-induced inflammation. Materials and methods The Ch-GNPs were conjugated with the PPARγ cDNA through a coacervation process. Conjugation was cast over Ti surfaces by dipping, and cells were seeded on different sizes (6 × 6 × 0.1 cm and 1 × 1 × 0.1 cm; n = 3) of Ti surfaces. The size of Ch- GNPs and surface characterization of Ti was performed using UV-vis spectroscopy, TEM (Transmission electron microscopy) and EDX (energy-dispersive X-ray). The DNA conjugation and transfection capacity of Ch- GNPs were simultaneously confirmed by agarose gel electrophoresis, β-galactosidase staining, and immunoblotting. Results The Ch- GNPs were well dispersed and spherical in shape, with average size around 10-20 nm. Ti surfaces coated with Ch- GNPs/LacZ, as transfection efficacy molecule, showed strong β-galactosidase staining in MC-3T3 E1 cells. Cells cultured on Ch- GNPs/ PPARγ-coated Ti surfaces were able to inhibit implant-induced inflammation by simultaneously suppressing the expression of tumor necrosis factor- alpha ( TNF-α), interleukin-1 beta ( IL-1β), inducible nitric oxide synthase ( iNOS), cyclooxygenase-2 ( COX-2), and matrix metalloproteinase-2 ( MMP-2). The inhibition mechanism of Ch- GNPs/ PPARγ was due to inhibition of both reactive oxygen species ( ROS) and nitric oxide ( NO) secretion ( n = 3; P < 0.05). In addition, Ch-GNPs/PPARγ was able to increase expression of bone morphogenetic protein (BMP-7) and runt-related transcription factor-2 ( RUNX-2). Furthermore, alkaline phosphatase activity ( ALP) was also increased than that in control ( n = 3; P < 0.01). Whereas, expression of receptor activator of NF-κB ligand ( RANKL) was decreased. Conclusions The novel gene delivery materials, like Ch- GNPs, can carry the PPARγ cDNA into the required areas of the implant surfaces, thus aiding to inhibit inflammation and promote osteoblast function. Thus, the PPARγ on implant surfaces may promote its clinical application on peri-implantitis or periodontitis like diseases. [ABSTRACT FROM AUTHOR]

Emerging evidence suggests that oncogenes play an important role in the inflammatory reactions in cancer cells, but the precise molecular and cellular mechanisms linking the oncogenes to inflammation is unclear. This study examined the contribution of proto-oncogene c-myb to inflammation in MCF-7 breast cancer cells. An inflammatory response was elicited directly by the cells using an in vitro culture system whereby the cells were exposed to H2O2. Upon exposure to H2O2, the cells showed a local inflammatory response, as evidenced by matrix metalloproteinases (MMPs) and ICAM-1 expression. Significant up-regulation of the proto-oncogene c-myb also was observed under inflammatory conditions. c-myb, overexpressed in the cells by transducing with Ad/c-myb, showed an increase in MMPs and ICAM-1 expression under H2O2 stimulation. Despite H2O2 stimulation, the c-myb down-regulated cells by c-myb siRNA inhibit the expression of MMPs and ICAM-1. Among the MAPKs, ERK1/2 and SAPK/JNK were activated by the H2O2 treatment. Interestingly, the H2O2-induced activation of ERK1/2 and SAPK/JNK was inhibited by siRNA c-myb. These results suggest that breast cancer cells may play a significant role in sustaining and amplifying the inflammation process through the activation of c-myb, which results in the activation of the ERK1/2 and SAPK/JNK pathway. This condition highlights the potential link between inflammation and its involvement in promoting breast cancer proliferation. Copyright © 2011 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Titanium is biocompatible with bodily tissues. However, the formation of ROS on the titanium surfaces might have negative response of the activity of the surroundings cells. Terrein was isolated from Penicullium sp. 20135 and found to reduce the effects of LPS-induced inflammation. This study examined the role of Terrein on the biocompatibility of titanium to determine if it can help improve osseointegration. MC-3T3 E1 cells were grown on titanium surfaces. The biocompatibility of Terrein was examined by adding it directly to the culture media at the indicated concentration. The cells on the titanium surface produced excessive ROS and decreased the activity of Cu/Zn SOD and Mn SOD. Moreover, the cells had higher activity towards oxidative stress molecules, such as MAPK, FAK and iNOS expression. In addition, MC-3T3 E1 osteoblast-like cells promoted osteoclast differentiation but reduced osteoblast differentiation and mineralization on the titanium surface. Interestingly, the cells given the Terrein treatment showed higher resistance towards oxidative stress through the up-regulation of ERK1/2 and FAK activity but the down-regulation of SAPK/JNK and iNOS activity. Moreover, Terrein promoted osteoblast differentiation and bone mineralization to elevate the activity of ALP, SPARC and down-regulate RANKL expression after blocking NF-κB translocation from the cytosol to the nucleus. In conclusion, the presence of Terrein on titanium surfaces increases osteoblast cell growth without inflammation. Moreover, Terrein, as a putative antioxidant agent, may enhance osseointegration by decreasing the level of ROS and having a potentially synergistic effect on osteoblast differentiation. Copyright © 2010 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The ageing of an inevitable life function is an unavoidable regressive physical process. Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor family. PPAR γ plays an important role in regulating several metabolic pathways. Recently, PPAR γ has been implicated in inflammatory responses and age-related diseases. The aim of this study was to determine the anti-inflammatory reaction of PPAR γ in an induced ageing progress. The late passage of human diploid fibroblasts (HDF), an in vitro ageing model, reveals the biological index materials of ageing. Aged cells showed decreased PPAR γ expression and elevated levels of intracellular adhesion molecule-1 (ICAM-1), an inflammatory molecule. To induce the aged cell phenotype, the middle stage of HDF cells (PD31) were induced stress induced premature senescence (SIPS) with 200 µM H2O2 for 2 h. SIPS-HDF cells showed high levels of ICAM-1, extracellular signal regulated kinase (ERK1/2) activity and matrix metallomatrix protease (MMP-2, -9) activity, and low levels of PPAR γ expression. A reconstitution of SIPS HDF cells with Ad/PPAR γ resulted in the downregulation of ICAM-1, ERK1/2, MMP-2 and -9, and normalized growth of SIPS-HDF cells. Moreover, PPAR γ in aged HDF cells reduced pro-inflammatory molecules and eliminated the formation of reactive oxygen species (ROS) through the ERK1/2 pathway. These results strongly suggest that PPAR γ plays a key role in age-related inflammation and may have clinical applications as a molecular target in the treatment of age-related inflammation. Copyright © 2010 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The stress-activated protein kinase/ c-Jun N-terminal kinase (SAPK/JNK) pathway is a well-known senescence-related stress activated protein kinase. Multiple environmental stresses induce programmed cell death, such as apoptosis. Normal human diploid fibroblast (HDF) cells have a limited life span in vitro, halting proliferation after a fixed number of cell divisions. Aged passage HDF showed resistance to oxidative stress involving heat shock proteins (Hsp60) through a mechanism involving the translocation of Hsp60 from the mitochondria to the cytosol. The present study showed that the translocation of Hsp60 from the mitochondria to the cytosol followed by high levels of p-SAPK/JNK activation as a result of oxidative stress was observed in the young cells only. The inhibition of SAPK/JNK activation by SP600125 under oxidative stress almost completely blocked the translocation of Hsp60 in both young and aged cells. This suggests that aged HDF cells are resistant to oxidative stress by blocking the translocation of Hsp60 from the mitochondria to the cytosol followed by SAPK/JNK inhibition. Overall, the mechanism of resistance by oxidative stress in aged cells is induced by blocked of the translocation of Hsp60 followed by SAPK/JNK inactivation. Copyright © 2008 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Paired box gene 9 ( Pax9) and c-myb are transcription factors that regulate the expression of the genes involved in mediating cell proliferation, resistance to apoptosis, and migration. However, the function of Pax9 in oral squamous cell carcinoma (OSCC) is virtually unknown. This study examined the anti-apoptotic roles of Pax9 and c-myb, and clarified interaction between the two genes in KB cells. Inhibition of Pax9 caused the induction of apoptosis with enhanced cleavage of caspase-3 and PARP, accelerated Bax, and reduced Bcl-2 expression. Transducing c-myb cells with adenovirus c-myb (Ad/ c-myb) were induced cell growth and inhibited apoptosis, but dominant-negative myb cells (Ad/DN- myb) were not affected. Pax9 was upregulated in the Ad/ c-myb cells with simultaneous decrease in the Ad/DN-myb infection. However, c-myb remained unaffected in the Pax9 small interfering RNA (siRNA) transfected cells. Moreover, the Pax9 siRNA transfected cells and Ad/DN- myb infected cells were able to arrest the cell cycle at the G0 phase. This suggests that Pax9 and c-myb expression in KB cells is essential for cell growth, and survival is enhanced by c-myb. Disrupting the function of c-myb and Pax9 could be a potential target for cancer treatment. Copyright © 2008 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Since an attenuated response to stress is a characteristic of senescence, a cellular senescence model was used to examine the mechanism of resistance against oxidative stress using human diploid fibroblasts (HDF). With increasing passage, the HDF showed increased production of reactive oxygen species (ROS). Late passage HDF were resistant to the lethal effects of oxidative stress, showing less cleavage of pro-caspase-3 and PARP than those of early ones. Since heat shock proteins (Hsps) are not only cytoprotective but also interfere with the apoptotic cascade, the expression patterns of Hsps during cellular senescence were next examined. Oxidative stress induced a decrease in the mitochondrial Hsp60 levels with a concomitant increase in the cytosolic Hsp60 levels in the early passage HDF, but not in late ones. To show that the resistance to oxidative stress is a specific effect of Hsp60, the levels of Hsp60 were knocked down by siRNA. As expected the Hsp60 knock-down cells were more resistant to oxidative stress. These findings show that Hsp60 is a key player in the resistance mechanism against oxidative stress and aging. Copyright © 2008 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The ageing of an inevitable life function is an unavoidable regressive physical process. Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor family. PPARgamma plays an important role in regulating several metabolic pathways. Recently, PPARgamma has been implicated in inflammatory responses and age-related diseases. The aim of this study was to determine the anti-inflammatory reaction of PPARgamma in an induced ageing progress. The late passage of human diploid fibroblasts (HDF), an in vitro ageing model, reveals the biological index materials of ageing. Aged cells showed decreased PPARgamma expression and elevated levels of intracellular adhesion molecule-1 (ICAM-1), an inflammatory molecule. To induce the aged cell phenotype, the middle stage of HDF cells (PD31) were induced stress induced premature senescence (SIPS) with 200 microM H(2)O(2) for 2 h. SIPS-HDF cells showed high levels of ICAM-1, extracellular signal regulated kinase (ERK1/2) activity and matrix metallomatrix protease (MMP-2, -9) activity, and low levels of PPARgamma expression. A reconstitution of SIPS HDF cells with Ad/PPARgamma resulted in the downregulation of ICAM-1, ERK1/2, MMP-2 and -9, and normalized growth of SIPS-HDF cells. Moreover, PPARgamma in aged HDF cells reduced pro-inflammatory molecules and eliminated the formation of reactive oxygen species (ROS) through the ERK1/2 pathway. These results strongly suggest that PPARgamma plays a key role in age-related inflammation and may have clinical applications as a molecular target in the treatment of age-related inflammation.