Revision Extension of Fusion Surgery in Thoracolumbar Spine Using a Newly Designed Revision Rod - Comparative Matched Cohort Study Versus Implant-Replacement Surgery.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To compare the results of revision extension of fusion surgery using the newly designed revision rod and implant-replacement surgery in thoracolumbar spine. METHODS: Thirty-one patients who underwent extension of fusion surgery using the revision rod for adjacent segment disease were included in this study. Thirty-one patients who underwent implant-replacement revision surgery were selected as a control group by matching age, sex, preoperative diagnosis, and number of revision segments. RESULTS: The mean age was 70.7 ± 8.0 years in the revision rod (RR) group and 69.0 ± 8.4 years in the control group. Preoperative diagnoses, underlying diseases, and mean number of revision segments (2.2 ± 1.1) were similar in both groups. The change of hemoglobin (1.0 ± 1.9 vs 2.5 ± 1.5 g/dl; P < .01), hematocrit (4.1 ± 4.9 vs 7.2 ± 4.4 % P < .01) and albumin (.8 ± .9 vs 1.3 ± .4 g/dl; P < .01) levels before and after surgery showed significant differences between the two groups. Hemovac drainage was significantly less in the RR group (P = .01). The mean operative time was shorter in the RR group (203.5 ± 9.5 min vs 233.5 ± 8.7 min; P = .12) with no statistical difference. Radiological results showed that the average lumbar lordosis 2 years after surgery was lower in the RR group compared to the control group (25.1 ± 9.9° vs 32.9 ± 9.8°; P = .02). Union rates and clinical outcomes were not different between the two groups. CONCLUSIONS: Revision extension of fusion surgery using a newly designed revision rod had less hemovac drainage and superior laboratory findings compared to implant-replacement revision surgery.

Sarcopenia in paraspinal muscle as a risk factor of proximal junctional kyphosis and proximal junctional failure after adult spinal deformity surgery.

OBJECTIVE: The aim of this study was to identify the risk factors for proximal junctional kyphosis (PJK) and proximal junctional failure (PJF), including paraspinal muscle atrophy. METHODS: Fifty-seven consecutive patients who underwent a long-instrumented fusion for adult spinal deformity (ASD) with a minimum follow-up of 2 years were included in the study. Patient, surgical, and radiological factors were evaluated. Muscle volume was measured using the muscle/vertebra ratio of the multifidus, erector spinae (ES), and psoas muscles, and muscle function was evaluated using the degree of fat infiltration at the L4-5 level. RESULTS: The study included 57 consecutive patients: 25 patients in the combined PJK/PJF group (13 with PJK and 12 with PJF) and 32 in the control group (without PJK or PJF). The mean time to onset of PJK and PJF was 15.7 and 1.7 months, respectively. Multivariate analysis showed that greater pre- and postoperative sagittal vertical axis was associated with the occurrence of PJK/PJF. ES muscle atrophy was more significant in the PJK/PJF group than in the control group, and more severe in the PJF than in the PJK group. CONCLUSIONS: This study showed that PJF occurred much earlier than PJK after ASD surgery. Paraspinal muscle atrophy was identified as a significant risk factor for PJK and PJF, especially PJF. The possibility of PJK and PJF development should be considered when long-segment fusion is planned for patients with paraspinal muscle atrophy.

A Multicenter Survey of Percutaneous Endoscopic Gastrostomy in 2019 at Korean Medical Institutions.

Background/Aims: : This study aimed to review the indications, methods, cooperation, complications, and outcomes of percutaneous endoscopic gastrostomy (PEG). Methods: : Questionnaires were sent to 200 hospitals, of which 62 returned their questionnaires, with a response rate of approximately 30%. Descriptive statistics were calculated to analyze the responses to the questionnaires. Results: : In 2019, a total of 1,052 PEGs were performed in 1,017 patients at 62 hospitals. The main group who underwent PEG was older adult patients with brain disease, particularly stroke. Nutritional supply was an important purpose of the PEG procedure. "The pull method" was the most commonly used for initial PEG insertion. The complications related to PEG were mostly mild, with leakage being the most common. Patients who underwent PEG procedures were primarily educated regarding the post-procedure management and complications related to PEG. Preoperative meetings were skipped at >50% of the institutions. Regarding the cooperation between the nutrition support team (NST) and the physician performing PEG, few endoscopists answered that they cooperated with NST before and after PEG. Moreover, the rate of NST certification obtained by physicians performing PEG and the frequency of attendance at NST-related conferences were relatively low. Conclusions: : This study shows a similar trend to that found in the previous PEG guidelines. However, it covers new aspects, including team-based work for PEG procedure, nutrition support, and education for patients and guardians. Therefore, each medical institution needs to select an appropriate method considering the medical environment and doctor's abilities.

Do Magnets Have the Potential to Serve as a Stabilizer for the Shoulder Joint in Massive Rotator Cuff Tears?: A Biomechanical Cadaveric Study.

Background: Disruption of the rotator cuff muscles compromises concavity compression force, which leads to superior migration of the humeral head and loss of stability. A novel idea of using the magnetic force to achieve shoulder stabilization in massive rotator cuff tears (MRCTs) was considered because the magnets can stabilize two separate entities with an attraction force. This study aimed to investigate the biomechanical effect of the magnetic force on shoulder stabilization in MRCTs. Methods: Seven fresh frozen cadaveric specimens were used with a customized shoulder testing system. Three testing conditions were set up: condition 1, intact rotator cuff without magnets; condition 2, an MRCT without magnets; condition 3, an MRCT with magnets. For each condition, anterior-posterior translation, superior translation, superior migration, and subacromial contact pressure were measured at 0°, 30°, and 60° of abduction. The abduction capability of condition 2 was compared with that of condition 3. Results: The anterior-posterior and superior translations increased in condition 2; however, they decreased compared to condition 2 when the magnets were applied (condition 3) in multiple test positions and loadings (p < 0.05). Abduction capability improved significantly in condition 3 compared with that in condition 2, even for less deltoid loading (p < 0.05). Conclusions: The magnet biomechanically played a positive role in stabilizing the shoulder joint and enabled abduction with less deltoid force in MRCTs. However, to ensure that the magnet is clinically applicable as a stabilizer for the shoulder joint, it is necessary to thoroughly verify its safety in the human body and to conduct further research on technical challenges.

Diagnostic value of serum procalcitonin and C-reactive protein in discriminating between bacterial and nonbacterial colitis: a retrospective study.

BACKGROUND: Differentiating between bacterial and nonbacterial colitis remains a challenge. We aimed to evaluate the value of serum procalcitonin (PCT) and C-reactive protein (CRP) in differentiating between bacterial and nonbacterial colitis. METHODS: Adult patients with three or more episodes of watery diarrhea and colitis symptoms within 14 days of a hospital visit were eligible for this study. The patients' stool pathogen polymerase chain reaction (PCR) testing results, serum PCT levels, and serum CRP levels were analyzed retrospectively. Patients were divided into bacterial and nonbacterial colitis groups according to their PCR. The laboratory data were compared between the two groups. The area under the receiver operating characteristic curve (AUC) was used to evaluate diagnostic accuracy. RESULTS: In total, 636 patients were included; 186 in the bacterial colitis group and 450 in the nonbacterial colitis group. In the bacterial colitis group, Clostridium perfringens was the commonest pathogen (n=70), followed by Clostridium difficile toxin B (n=60). The AUC for PCT and CRP was 0.557 and 0.567, respectively, indicating poor discrimination. The sensitivity and specificity for diagnosing bacterial colitis were 54.8% and 52.6% for PCT, and 52.2% and 54.2% for CRP, respectively. Combining PCT and CRP measurements did not increase the discrimination performance (AUC, 0.522; 95% confidence interval, 0.474-0.571). CONCLUSION: Neither PCT nor CRP helped discriminate bacterial colitis from nonbacterial colitis.

Global Sagittal Alignment and Clinical Outcomes after 1-3 Short-Segment Lumbar Fusion in Degenerative Spinal Diseases.

STUDY DESIGN: Level III retrospective study. PURPOSE: We investigated the impact of short-segment lumbar fusion on the restoration of global sagittal alignment and the correlations between spino-pelvic parameters and clinical outcomes. OVERVIEW OF LITERATURE: Sagittal imbalance leads to energy consumption and pain in maintaining a standing position. For adult spinal deformity, it is critical to create optimal lumbar lordosis (LL) in order to achieve restoration of sagittal imbalance. However, surgeons do not pay attention to correcting LL in short-segment lumbar fusion. METHODS: A total of 69 patients with transforaminal lumbar interbody fusion (TLIF) for degenerative spinal disease were evaluated with a minimum 2-year follow-up. All patients underwent TLIF with hyper-lordotic angle cages to achieve higher LL. Radiological spino-pelvic parameters including sagittal vertical axis (SVA) and clinical outcomes using the Oswestry Disability Index (ODI) and Numeric Rating Scale (NRS) were evaluated. RESULTS: The average LL was 35.8°±9.9° before surgery, 42.3°±9.3° 1 year after surgery, and 40.3°±10.2° 2 years after surgery (p <0.01). The average SVA was 43.1±6.2 mm before surgery, 21.2±4.9 mm 1 year after surgery, and 34.0±4.7 mm 2 years after surgery (p <0.01). The average LL and SVA improved in two- or three-segment fusion, but not in one-segment fusion. The correlation between ΔLL and ΔSVA was significant in all segment fusions. The correlation between ΔLL and ΔSVA was more significant at the L4-5 and L5-S1 segments than at L3-4. ODI was significantly correlated with SVA (p <0.05). NRS showed no correlation with the radiological parameters. CONCLUSIONS: Two- or three-segment lumbar fusion using hyper-lordotic angle cages improved LL and SVA. A significant correlation between the correction of LL and SVA was found. Higher correction of LL using hyper-lordotic angle cages is thus recommended in short-segment lumbar fusion, since postoperative improvements of SVA significantly affect clinical outcomes.

Guided bone regeneration with a gelatin layer and adenoviral delivery of c-myb enhances bone healing in rat tibia.

Aim: Bone healing becomes problematic during certain states, such as trauma. This study verifies whether the application of c-myb with gelatin promotes bone healing during bone injuries. Materials & methods: A biodegradable membrane was modified with adenoviral vector c-myb (Ad/c-myb) and gelatin and applied in the bone injury site of rat tibia. Results:c-myb enhanced osteogenic differentiation and mineralization in bone marrow stromal cells after induction with osteogenic media. In vivo examination of rat tibia after application of the biodegradable membrane with Ad/c-myb and a gelatin layer demonstrated increased bone volume, bone mineral density, new bone formation and osteogenic molecules, compared with Ad/LacZ. Conclusion:c-myb has the potential to assist bone healing and may be applicable to the treatment of bone during injury.

Comparison of Bone Marrow Aspirate Concentrate and Allogenic Human Umbilical Cord Blood Derived Mesenchymal Stem Cell Implantation on Chondral Defect of Knee: Assessment of Clinical and Magnetic Resonance Imaging Outcomes at 2-Year Follow-Up.

Biological repair of cartilage lesions remains a significant clinical challenge. A wide variety of methods involving mesenchymal stem cells (MSCs) have been introduced. Because of the limitation of the results, most of the treatment methods have not yet been approved by the Food and Drug Administration (FDA). However, bone marrow aspirate concentrate (BMAC) and human umbilical cord blood derived mesenchymal stem cells (hUCB-MSCs) implantation were approved by Korea FDA. The aim of this study was to evaluate clinical and magnetic resonance imaging (MRI) outcomes after two different types of MSCs implantation in knee osteoarthritis. Fifty-two patients (52 knees) who underwent cartilage repair surgery using the BMAC (25 knees) and hUCB-MSCs (27 knees) were retrospectively evaluated for 2 years after surgery. Clinical outcomes were evaluated according to the score of visual analogue scale (VAS), the International Knee Documentation Committee (IKDC) subjective, and the Knee Injury and Osteoarthritis Outcome Score (KOOS). Cartilage repair was assessed according to the modified Magnetic Resonance Observation of Cartilage Repair Tissue (M-MOCART) score and the International Cartilage Repair Society (ICRS) cartilage repair scoring system. At 2-year follow-up, clinical outcomes including VAS, IKDC, and KOOS significantly improved (P < 0.05) in both groups; however, there were no differences between two groups. There was no significant difference in M-MOCART [1-year (P = 0.261), 2-year (P = 0.351)] and ICRS repair score (P = 0.655) between two groups. Both groups showed satisfactory clinical and MRI outcomes. Implantation of MSCs from BMAC or hUCB-MSCs is safe and effective for repairing cartilage lesion. However, large cases and a well-controlled prospective design with long-term follow-up studies are needed.

Effects of Swimming Exercise on Serum Irisin and Bone FNDC5 in Rat Models of High-Fat Diet-Induced Osteoporosis.

This study aimed to investigate the expression of PGC-1α/FNDC5/irisin induced by attenuation of high-fat diet (HFD)-induced bone accrual and determine whether swimming exercise could improve attenuating bone accrual through this mechanism. Eight-week-old Sprague-Dawley rats were divided into two groups for the first 8 weeks: CD, control diet (n = 10); and HFD, high-fat diet (n = 20). HFD-fed rats were again divided into two groups for further 8 weeks treatment: HFD (n = 10) and HFD with swimming exercise (HEx, n = 10). During this time, the CD group continuously fed the normal diet. Throughout the 16 weeks study period, the rats were weighed once every week. Samples were collected for analysis after last 8 weeks of treatment in the 16 weeks. Morphological and structural changes of the femur and tibial bone were observed using micro-CT, and Osteocalcin, CTX-1 and irisin levels in the blood were measured by enzyme-linked immunosorbent assay. The expression of IL-1, ß-catenin, FNDC5 and PGC-1α, in the femur were evaluated by immunohistochemistry. Eight weeks of HFD increased body weight and epididymal fat mass and decreased bone mineral density (BMD). Subsequent 8 weeks of swimming exercise improved obesity, BMD, bone microstructure, and bone metabolic factors in the HEx group. The irisin levels in the blood and the expressions of FNDC5 and PGC-1α in the bone were significantly lower in the HFD group than in the CD group, but elevated in the HEx group than in the HFD group. Swimming exercise is effective in improving obesity-worsened bone health and increases blood irisin and bone PGC-1α and FNDC5 levels.

Schisandra chinensis extract ameliorates age-related muscle wasting and bone loss in ovariectomized rats.

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, ß-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.

A universal ultrasound diagnostic system developed to support urology and coloproctological applications.

In this study, we sought to describe a novel imaging apparatus that is lightweight, inexpensive, and highly effective for use in colorectal diagnostic and treatment settings. Typical probes for use in colorectal ultrasonic imaging applications are developed for surgeons to diagnose and stage rectal tumors and image the rectum and anus. Here we outline a new technique and use it for colorectal imaging in an animal. This technique involves use of an ultrasound array module positioned along the axis of rotation such that improved rotation is possible. This module is in the shape of a linear rod with a rotary linear component that allows for emission of focused ultrasonic echo signals from a linear section of the probe. The usability of the transducer and rectal image quality are satisfactory in a porcine model with the technique proposed here, axial/lateral resolution as 0.96/2.24 mm with 6 dB applied through the contour map using the point spread function. When compared to currently available methods, this technique provides superior diagnostic 3D volumetric image quality with reduced acquisition time. Given this, the ultrasound device proposed here may prove a viable and preferable method to those currently available for urology and colorectal imaging applications.

Interval running training improves age-related skeletal muscle wasting and bone loss: Experiments with ovariectomized rats.

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. ABSTRACT: 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.

Chitosan-gold nanoparticles mediated gene delivery of c-myb facilitates osseointegration of dental implants in ovariectomized rat.

Osseointegration of dental implants is affected by osteoporosis. The purpose of this study was overcome the implant failure and facilitate the osseointegration of dental implants by c-myb in ovariectomized (OVX)-induced osteoporosis. c-myb is a transcription factor and supports bone formation. Plasmid DNA/c-myb conjugated with chitosan-gold nanoparticles (Ch-GNPs/c-myb) promoted osteogenesis and inhibited osteoclastogenesis in MC-3T3 E1 cells. Ch-GNPs/c-myb involved the reduction of the nuclear factor of activated T-cells 1, c-Fos, and tartrate-resistant acid phosphatase-positive multinucleated osteoclasts in receptor activator of nuclear factor-κB ligand (RANKL) stimulated bone marrow macrophages. In vivo results of rat mandibles demonstrated Ch-GNP/c-myb-coated titanium (Ti) implants increased the volume and density of newly formed bone and the osseointegration of dental implant with bone by micro computed tomography examination after OVX-induced osteoporosis. Immunohistochemical analysis showed increased c-myb expression and upregulation of bone morphogenic proteins, osteoprotegerin and EphB4, as well as the downregulation of RANKL by Ch-GNP/c-myb-coated Ti implants. Hematoxylin and Eosin staining expressed new bone formation by Ch-GNP/c-myb-coated Ti implants. Our findings indicated that c-myb delivered by Ch-GNPs supports osseointegration of dental implant even in osteoporotic condition. c-myb may be applicable to support dental implant integration and treatment in age-dependent bone destruction disease.

Phelligridin D-loaded oral nanotube titanium implant enhances osseointegration and prevents osteolysis in rat mandible.

Poor bone quality and osteolysis are the major causes of implant failure in dentistry. Here, this study tested the effect of phelligridin D-loaded nanotubes titanium (Ti) for bone formation around the dental implants. The purpose of this study was to enhance osseointegration of phelligridin D-loaded implant into the bone for bone formation and prevention of osteolysis. Cell viability, crystal violet staining, Western blot, alizarin red S staining, alkaline phosphatase activity, tartrate-resistant acid phosphatase staining, micro-computed tromography (µ-CT), hematoxylin and eosin (H&E) and immunohistochemical staining were used in vitro and in vivo to test the biocompatibility of phelligridin D. Phelligridin D enhanced osteoblast differentiation and mineralization by increasing bone morphogenic protein-2/7 (BMP-2/7), Osterix, Runx-2, osteoprotegerin (OPG), alkaline phosphatase and inhibited osteoclast differentiation by decreasing receptor activator of nuclear factor kappa-B ligand (RANKL) in MC-3T3 E1 cells. Further, phelligridin D promoted bone regeneration around nanotube Ti implant surface by increasing the levels of BMP-2/7 and OPG in a rat model. Phelligridin D also inhibited osteolysis by suppressing the expression of RANKL. These findings strongly suggest that phelligridin D is a new compound representing a potential therapeutic candidate for implant failure caused by osteolysis and poor bone quality of teeth.

Schisandrin C enhances odontoblastic differentiation through autophagy and mitochondrial biogenesis in human dental pulp cells.

OBJECTIVE: To investigate the role of Schisandrin C in odontoblastic differentiation, and its relations between autophagy and mitochondrial biogenesis in human dental pulp cells (HPDCs). DESIGN: Fresh third molars were used, and cultured for HDPCs. Western blotting technique, Alizarin red S staining, alkaline phosphatase (ALP) activity, and confocal microscopy were used to detect autophagy, mitochondrial biogenesis, and odontoblastic differentiation. To understand the mechanism of Schisandrin C, the HDPCs were treated with lipopolysaccharide (LPS), autophagy and heme oxygenase-1 (HO-1) inhibitors: 3-Methyladenine (3-MA) and Zinc protoporphyrin IX (ZnPP), respectively. RESULTS: LPS decreased the expression of autophagy molecules [autophagy protein 5 (ATG-5), beclin-1, and microtubule-associated protein 1A/1B light chain 3 (LC3-I/II)] and mitochondrial biogenesis molecules [heme oxygenase-1 (HO-1) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α)], and disrupted odontoblastic differentiation. The down-regulation of autophagy and mitochondrial biogenesis with 3-MA and ZnPP inhibited odontoblastic differentiation. However, Schisandrin C restored the expression of all the above molecules, even with LPS and inhibitor treatment. This result demonstrates that autophagy and mitochondrial biogenesis plays an essential role in odontoblastic differentiation, and Schisandrin C activates these systems to promote odontoblastic differentiation of HDPCs. CONCLUSION: Schisandrin C has potential characters to regulate odontoblastic differentiation, and may be recommended for use as a compound for pulp homeostasis.

Gomisin A modulates aging progress via mitochondrial biogenesis in human diploid fibroblast cells.

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.

Schisandrin C enhances mitochondrial biogenesis and autophagy in C2C12 skeletal muscle cells: potential involvement of anti-oxidative mechanisms.

The molecular study of muscles is needed to overcome chronic inflammation and maintenance of muscles in the human body. Schisandrin C is a pharmacological compound derived from the fruit of Schisandra chinensis and has many characteristics including anti-inflammation, anti-tumor, and anti-oxidation. However, the cellular and molecular mechanisms of Schisandrin C are still not well understood especially in skeletal muscle. Therefore, the present study was evaluated whether the properties of Schisandrin C in C2C12 skeletal muscle cells involved maintenance of cellular homeostasis and protection against oxidative damage. Differentiated C2C12 cells were exposed to H2O2 to induce oxidative stress. The characteristics of anti-oxidants, anti-inflammation, autophagy, and mitochondrial biogenesis were tested by Western blotting. Confocal microscopy was also used to observe mitochondrial activity. Schisandrin C inhibited inflammatory molecules with enhancing anti-oxidant activity and reducing reactive oxygen species (ROS) even in the presence of H2O2. The dual anti-inflammation and anti-oxidant roles of Schisandrin C regulated the translocation of nuclear factor kappa B (NF-κB) and nuclear factor erythroid 2-related factor-2 (Nrf-2) to nucleus followed by inhibition of the mitogen-activated protein kinase (MAPK) pathway. Schisandrin C promoted the expression of autophagy and mitochondrial biogenesis molecules. Furthermore, the effect of Schisandrin C increased the mitochondrial activity against oxidative stress. Consequently, the action of Schisandrin C enhanced the regulation of autophagy and mitochondrial biogenesis with potential involvement of anti-oxidative mechanisms including the MAPKs/Nrf-2/heme oxygenase-1 signaling pathway in C2C12 skeletal muscle cells exposed to oxidative stress. Therefore, Schisandrin C may be considered as a beneficial compound for several muscle inflammations.

The effects of downhill and uphill exercise training on osteogenesis-related factors in ovariectomy-induced bone loss.

PURPOSE: Recent evidence suggests that regular exercise training plays a decisive role in maintaining homeostasis and promoting muscle and skeletal formation. However, the effect of downhill exercise training on osteogenesis-related factors is not well understood. METHODS: Thus, we investigated the effect of uphill and downhill training on ovariectomy (OVX)-induced bone loss. After ovary removal, the exercise method performed included uphill (16 m/min, +15°) and downhill training (16 m/min, -15°) for 60 min/day and 5 days/week, respectively, for 8 weeks. RESULTS: Our results showed that both uphill and downhill training significantly decreased the body weight, total cholesterol, and creatine kinase (CK) levels in the context of OVX-induced bone loss. On the contrary, levels of an osteogenesis indicator, osteocalcin and alkaline phosphatase were elevated. Consequently, the uphill and downhill training reduced OVX- induced bone loss in the distal femoral metaphysis. Likewise, the bone microstructure in OVX-induced bone loss was enhanced upon training. In particular, the inhibition of RANKL-induced osteoclast formation and osteoclast-specific gene expression improved upon downhill training compared to uphill training. CONCLUSION: These results suggest that the uphill and downhill exercise types appeared to positively affect the expression of osteogenesis-related factors along with bone density and microstructure. Particularly, the downhill training has more beneficial effects on the maintenance of homeostasis during bone formation.

Nanoparticle mediated PPARγ gene delivery on dental implants improves osseointegration via mitochondrial biogenesis in diabetes mellitus rat model.

Diabetes mellitus (DM) has a detrimental effect on osseointegration, stability and longevity of implants due to osteoporosis. In this study, PPARγ-loaded dental implants were investigated for the improvement of osseointegration and peri-implantitis. Chitosan gold nanoparticles conjugated with PPARγ cDNA were introduced on titanium mini-implant surfaces for PPARγ release to rat mandibular. DM-induced rat mandible showed structural changes such as decreased bone mass and increased inflammatory molecules, and diminution of PPARγ expression and bone formation molecules compared to normal rats. PPARγ induced bone formation via reduction of inflammatory molecules even under glucose oxidative stress. Furthermore, PPARγ strongly activated mitochondrial biogenesis and cell viability via p-AMK and Wnt/ß-catenin signaling. Consequently, PPARγ gene delivery on regional dental implants contributed osseointegration, new bone formation and mineralization in DM-induced rats. This study demonstrates that PPARγ can be used as a therapeutic gene with dental implantation in diabetic patients since regional PPARγ expression enhances osseointegration and implant longevity.

PPARγ regulates inflammatory reaction by inhibiting the MAPK/NF-κB pathway in C2C12 skeletal muscle cells

Excessive exercise induces an inflammatory response caused by oxidative stress, which delays recovery of damaged muscle fibers. The reduction of inflammatory response is important for skeletal muscle homeostasis. Peroxisome proliferator-activated receptor gamma (PPARγ) is an anti-inflammatory molecule, but the role of PPARγ in skeletal muscle as anti-inflammatory activity is not clear. Thus, this study examined the anti-inflammatory role of PPARγ against H2O2-induced oxidative stress in skeletal muscle. Sprague Dawley (SD) rats were exercised on a treadmill to induce oxidative stress. In vitro oxidative stress was evaluated in differentiated C2C12 cells stimulated using 200 μM H2O2. Inflammation-related molecules were determined by immunohistochemistry and Western blot analysis. Expressions of the inflammatory molecules tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), cyclooxygenase-2 (COX-2), and matrix metalloproteinase-2 (MMP-2) in muscles of the acute exercise group were highly increased. PPARγ was also highly expressed in these muscles. These inflammatory molecules were also markedly increased in C2C12 cells with H2O2 stimulation. However, PPARγ overexpression in C2C12 transfected by Ad/PPARγ dramatically reduced the inflammatory molecules. PPARγ also enhanced the anti-oxidants molecules like Cu/Zn-SOD, Mn-SOD, and hemeoxygenase-1 by reducing the generation of ROS, even in the presence of H2O2. PPARγ displayed dual anti-inflammatory and anti-oxidant roles by inhibiting the mitogen-activated protein kinase (MAPK) pathway and translocation of nuclear transcriptional factor-κB (NF-κB) from the cytosol to the nucleus. These results demonstrate a potential role of PPARγ in protecting muscle fibers against oxidative stress caused by excessive acute exercise due to its anti-inflammatory and anti-oxidant activity exerted by inhibition of the MAPK/NF-κB pathway (AU)

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