Inonotus obliquus upregulates muscle regeneration and augments function through muscle oxidative metabolism.

Skeletal muscle wasting related to aging or pathological conditions is critically associated with the increased incidence and prevalence of secondary diseases including cardiovascular diseases, metabolic syndromes, and chronic inflammations. Much effort is made to develop agents to enhance muscle metabolism and function. Inonotus obliquus (I. obliquus; IO) is a mushroom popularly called chaga and has been widely employed as a folk medicine for inflammation, cardiovascular diseases, diabetes, and cancer in Eastern Europe and Asia. However, its effect on muscle health has not been explored. Here, we aimed to investigate the beneficial effect of IO extract in muscle regeneration and metabolism. The treatment of IO in C2C12 myoblasts led to increased myogenic differentiation and alleviation of dexamethasone-induced myotube atrophy. Network pharmacological analysis using the identified specific chemical constituents of IO extracts predicted protein kinase B (AKT)-dependent mechanisms to promote myogenesis and muscle regeneration. Consistently, IO treatment resulted in the activation of AKT, which suppressed muscle-specific ubiquitin E3 ligases induced by dexamethasone. IO treatment in mice improved the regeneration of cardiotoxin-injured muscles accompanied by elevated proliferation and differentiation of muscle stem cells. Furthermore, it elevated the mitochondrial content and muscle oxidative metabolism accompanied by the induction of peroxisome proliferator-activated receptor γ coactivator α (PGC-1α). Our current data suggest that IO is a promising natural agent in enhancing muscle regenerative capacity and oxidative metabolism thereby preventing muscle wasting.

Decellularized human pancreatic extracellular matrix-based physiomimetic microenvironment for human islet culture.

A strategy that seeks to combine the biophysical properties of inert encapsulation materials like alginate with the biochemical niche provided by pancreatic extracellular matrix (ECM)-derived biomaterials, could provide a physiomimetic pancreatic microenvironment for maintaining long-term islet viability and function in culture. Herein, we have demonstrated that incorporating human pancreatic decellularized ECM within alginate microcapsules results in a significant increase in Glucose Stimulation Index (GSI) and total insulin secreted by encapsulated human islets, compared to free islets and islets encapsulated in only alginate. ECM supplementation also resulted in long-term (58 days) maintenance of GSI levels, similar to that observed in free islets at the first time point (day 5). At early time points in culture, ECM promoted gene expression changes through ECM- and cell adhesion-mediated pathways, while it demonstrated a mitochondria-protective effect in the long-term. STATEMENT OF SIGNIFICANCE: The islet isolation process can damage the islet extracellular matrix, resulting in loss of viability and function. We have recently developed a detergent-free, DI-water based method for decellularization of human pancreas to produce a potent solubilized ECM. This ECM was added to alginate for microencapsulation of human islets, which resulted in significantly higher stimulation index and total insulin production, compared to only alginate capsules and free islets, over long-term culture. Using ECM to preserve islet health and function can improve transplantation outcomes, as well as provide novel materials and platforms for studying islet biology in microfluidic, organ-on-a-chip, bioreactor and 3D bioprinted systems.

BST204, a Rg3 and Rh2 Enriched Ginseng Extract, Upregulates Myotube Formation and Mitochondrial Function in TNF-α-Induced Atrophic Myotubes.

The loss of skeletal muscle mass and function is a serious consequence of chronic diseases and aging. BST204 is a purified ginseng (the root of Panax ginseng) extract that has been processed using ginsenoside-ß-glucosidase and acid hydrolysis to enrich ginsenosides Rg3 and Rh2 from the crude ginseng. BST204 has a broad range of health benefits, but its effects and mechanism on muscle atrophy are currently unknown. In this study, we have examined the effects and underlying mechanisms of BST204 on myotube formation and myotube atrophy induced by tumor necrosis factor-α (TNF-α). BST204 promotes myogenic differentiation and multinucleated myotube formation through Akt activation. BST204 prevents myotube atrophy induced by TNF-α through the activation of Akt/mTOR signaling and down-regulation of muscle-specific ubiquitin ligases, MuRF1, and Atrogin-1. Furthermore, BST204 treatment in atrophic myotubes suppresses mitochondrial reactive oxygen species (ROS) production and regulates mitochondrial transcription factors such as NRF1 and Tfam, through enhancing the activity and expression of peroxisome proliferator-activated receptor-γ coactivator1α (PGC1α). Collectively, our findings indicate that BST204 improves myotube formation and PGC1α-mediated mitochondrial function, suggesting that BST204 is a potential therapeutic or neutraceutical remedy to intervene muscle weakness and atrophy.

KMRC011, an agonist of toll-like receptor 5, mitigates irradiation-induced tissue damage and mortality in cynomolgus monkeys.

In the study here, the potential applicability of KMRC011 - an agonist of toll-like receptor-5 - as a countermeasure for radiation toxicities was evaluated. Following a single 5.5 Gy total body irradiation (TBI, surface absorbed dose = 7 Gy) of Co60 γ-rays, mortality rates and degrees of pathological lesions that developed over 80 days were compared in monkeys that received TBI only and a group that was injected once with KMRC011 (10 µg/kg) after TBI. Compared to the TBI-only hosts (80%), the death rate was significantly improved by the use of KMRC011 (40%), all deaths in both groups occurred in the period from Days 19-24 post-TBI. Further analysis of monkeys that survived until the end of the experiment showed that AST and ALT levels were elevated only in the TBI group, and that radiation-induced tissue damage was alleviated by the KMRC011 injection. Additionally, expression of cell death-related proteins was lower in tissues from the KMRC011-treated hosts than in those in the TBI-only group. Other measured parameters, including body weight, food uptake, and hematological values did not significantly differ between the two groups over the entire period. The results of this study, thus demonstrate that KMRC011 could potentially be used as a medical countermeasure for the treatment of acute radiation exposure.

Ginsenoside Rg3 upregulates myotube formation and mitochondrial function, thereby protecting myotube atrophy induced by tumor necrosis factor-alpha.

ETHNOPHARMACOLOGICAL RELEVANCE: Ginsenoside Rg3 from Panax ginseng has reported to have multiple pharmacological activities including anti-diabetics, anti-inflammation and anti-cancer. However, the effect of ginsenoside Rg3 on myogenic differentiation and muscle atrophy is unknown. AIM TO THE STUDY: In this study, we investigated the myogenic effect and underlying molecular mechanisms of ginsenoside Rg3 on myotube atrophy induced by tumor necrosis factor-α (TNF-α). MATERIALS AND METHODS: C2C12 myoblasts were induced to differentiate for one day followed by the treatment of TNF-α along with vehicle or ginsenoside Rg3 for additional 2 days and subjected to immunoblotting, immunocytochemistry, quantitative RT-PCR and biochemical analysis for mitochondrial function. RESULTS: Ginsenoside Rg3 promotes myogenic differentiation and multinucleated myotube formation through Akt activation in a dose-dependent manner, without any cytotoxicity. Ginsenoside Rg3 treatment restores myotube formation and increases myotube diameters under TNF-α-treated conditions. Ginsenoside Rg3 enhances Akt/mTOR (mammalian target of rapamycin) signaling that in turn stimulates muscle-specific gene expression such as myosin heavy chain (MHC) and Myogenin, and suppresses the expression of muscle-specific ubiquitin ligases. In addition, ginsenoside Rg3 in TNF-α-treated myotubes significantly inhibits the production of mitochondrial ROS and restores mitochondrial membrane potential (MMP) and ATP contents. Furthermore, ginsenoside Rg3 upregulates the activities and expression of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α) and the mitochondrial biogenetic transcription factors, nuclear respiratory factor-1 (NRF1) and mitochondrial transcription factor A (Tfam) in TNF-α-induced myotube atrophy. CONCLUSIONS: This study provides a mechanistic insight into the effect of ginsenoside Rg3 on myogenic differentiation and myotube atrophy, suggesting that ginsenoside Rg3 has a promising potential as a therapeutic or neutraceutical remedy to intervene muscle weakness and atrophy.

Simple and facile preparation of recombinant human bone morphogenetic protein-2 immobilized titanium implant via initiated chemical vapor deposition technique to promote osteogenesis for bone tissue engineering application.

Over the past few decades, titanium (Ti) implants have been widely used to repair fractured bones. To promote osteogenesis, immobilization of osteoinductive agents, such as recombinant human bone morphogenic protein-2 (rhBMP2), onto the Ti surface is required. In this study, we prepared rhBMP2 immobilized on glycidyl methacrylate (GMA) deposited Ti surface through initiated chemical vapor deposition (iCVD) technique. After preparation, the bio-functionalized Ti surface was characterized by physicochemical analysis. For in vitro analysis, the developed Ti was evaluated by cell proliferation, alkaline phosphatase activity, calcium deposition, and real-time polymerase chain reaction to verify their osteogenic activity against human adipose-derived stem cells (hASCs). The GMA deposited Ti surface was found to effectively immobilize a large dose of rhBMP2 as compared to untreated Ti. Additionally, rhBMP2 immobilized on Ti showed significantly enhanced osteogenic differentiation and increased calcium deposition with nontoxic cell viability. These results clearly confirm that our strategy may provide a simple, solvent-free strategy to prepare an osteoinductive Ti surface for bone tissue engineering applications.

Canadine from Corydalis turtschaninovii Stimulates Myoblast Differentiation and Protects against Myotube Atrophy.

Cachexia and sarcopenia are the main causes of muscle atrophy. These result in a reduction in the muscle fiber area, myo-protein content, and muscle strength, with various molecular modulators being involved. Although several reports have proposed potential therapeutic agents, no effective treatments have been found for muscle atrophy. We searched for myogenic modulators from medicinal plants to treat muscle diseases. We isolated six alkaloids from Corydalis turtschaninovii and evaluated their myogenic potential by using the MyoD reporter gene assay in C2C12 cells. Among the tested compounds, canadine showed the strongest transactivation of MyoD and increased MHC expression during myogenesis. The activation of p38 MAP kinase and Akt are major mechanisms that contribute to the myogenesis by canadine. Canadine increased the number of multinucleated and cylinder-shaped myotubes during myogenesis of C2C12 myoblasts. To determine the preventive effect of canadine in cancer-induced muscle wasting, differentiated C2C12 myotubes were treated with conditioned media from CT26 colon carcinoma culture (CT26 CM) in the presence of canadine. Canadine ameliorated the muscle protein degradation caused by CT26-CM by down-regulating the muscle specific-E3 ligases, MAFbx/atrogin-1 and MuRF1. In this study, we found that canadine from C. turtschaninovii stimulates myogenesis and also inhibits muscle protein degradation. Therefore, we suggest canadine as a protective agent against muscle atrophy.

Predisposing Factors of Ischemic Colitis: Data from 14 Years of Experience in a Single Center.

BACKGROUND AND AIMS: While several case reports on ischemic colitis (IC) suggest the presence of predisposing causative factors, a few studies have investigated the predisposing factors in IC. This study aimed to identify the characteristics of patients with IC, particularly focusing on the predisposing factors. METHODS: We conducted a single-center, retrospective analysis of 159 patients with IC. Clinical characteristics, laboratory data, endoscopic findings, and medical records were reviewed. Data were compared between groups of patients defined according to the predisposing factors. The predisposing factors are defined as temporary states or episodic events occurring within a week before the development of IC such as colonoscopy, enema, use of laxatives, heavy drinking, pancreatitis, shock, and burn. RESULTS: Compared to the group of patients without predisposing factors of IC, the group of patients with predisposing factors was characterized by a relatively higher prevalence of male sex (56.9% versus 33.3%, p = 0.005), younger age (60.9 ± 15.4 versus 67.2 ± 13.4 years, p = 0.010), lower incidence of hypertension (43.1% versus 60.2%, p = 0.044), and fewer risk factors (1.24 ± 1.18 versus 1.82 ± 1.22, p = 0.005). CONCLUSIONS: Among men with predisposing factors, IC may develop even at a relatively younger age and in the absence of multiple risk factors, suggesting that predisposing factors may be involved in the pathogenesis of IC.

Isoquinoline alkaloids from Coptis japonica stimulate the myoblast differentiation via p38 MAP-kinase and Akt signaling pathway.

To overcome the muscle atrophy, such as cachexia and sarcopenia, we tried to find myogenic agents from medicinal plants. From myogenic extract of Coptis japonica, we purified six isoquinoline alkaloids and evaluated their effects on transactivation of myoD and MHC expression in C2C12 cells during differentiation process. Among obtained compounds, magnoflorine most efficiently enhanced the myoblast differentiation by activating the p38 MAP kinase and Akt pathway, and also increased the number of multinucleated and cylinder-shaped myotubes. These results propose that magnoflorine from Coptis japonica might be a promising lead compound for the development of anti-muscle atrophy drug.

Dehydrocorydaline promotes myogenic differentiation via p38 MAPK activation.

Muscle regeneration is a coordinated process that involves proliferation and differentiation of muscle progenitor cells. Activation of MyoD is a key event in myogenic differentiation, which is regulated by p38 mitogen­activated protein kinases (MAPK). In a screen of natural compounds for the enhancement of MyoD activity, dehydrocorydaline (DHC) from the Corydalis tuber was identified. Treatment of C2C12 myoblasts with DHC increased the expression levels of muscle­specific proteins, including MyoD, myogenin and myosin heavy chain. In addition, C2C12 myoblasts exhibited enhanced multinucleated myotube formation without any cytotoxicity. Treatment with DHC elevated p38 MAPK activation and the interaction of MyoD with an E protein, which is likely to result in activation of MyoD and promotion of myoblast differentiation. Furthermore, defects in differentiation­induced p38 MAPK activation and myoblast differentiation induced by depletion of the promyogenic receptor protein Cdo in C2C12 myoblasts were restored by DHC treatment. In conclusion, these results indicated that DHC stimulates p38 MAPK activation, which can enhance heterodimerization of MyoD and E proteins, thus resulting in MyoD activation and myoblast differentiation. These findings suggested that DHC may be considered a potential therapeutic compound for the improvement of muscle stem cell regenerative capacity in injured muscle.

Improving gastric cancer preclinical studies using diverse in vitro and in vivo model systems.

BACKGROUND: "Biomarker-driven targeted therapy," the practice of tailoring patients' treatment to the expression/activity levels of disease-specific genes/proteins, remains challenging. For example, while the anti-ERBB2 monoclonal antibody, trastuzumab, was first developed using well-characterized, diverse in vitro breast cancer models (and is now a standard adjuvant therapy for ERBB2-positive breast cancer patients), trastuzumab approval for ERBB2-positive gastric cancer was largely based on preclinical studies of a single cell line, NCI-N87. Ensuing clinical trials revealed only modest patient efficacy, and many ERBB2-positive gastric cancer (GC) patients failed to respond at all (i.e., were inherently recalcitrant), or succumbed to acquired resistance. METHOD: To assess mechanisms underlying GC insensitivity to ERBB2 therapies, we established a diverse panel of GC cells, differing in ERBB2 expression levels, for comprehensive in vitro and in vivo characterization. For higher throughput assays of ERBB2 DNA and protein levels, we compared the concordance of various laboratory quantification methods, including those of in vitro and in vivo genetic anomalies (FISH and SISH) and xenograft protein expression (Western blot vs. IHC), of both cell and xenograft (tissue-sectioned) microarrays. RESULTS: The biomarker assessment methods strongly agreed, as did correlation between RNA and protein expression. However, although ERBB2 genomic anomalies showed good in vitro vs. in vivo correlation, we observed striking differences in protein expression between cultured cells and mouse xenografts (even within the same GC cell type). Via our unique pathway analysis, we delineated a signaling network, in addition to specific pathways/biological processes, emanating from the ERBB2 signaling cascade, as a potential useful target of clinical treatment. Integrated analysis of public data from gastric tumors revealed frequent (10 - 20 %) amplification of the genes NFKBIE, PTK2, and PIK3CA, each of which resides in an ERBB2-derived subpathway network. CONCLUSION: Our comprehensive bioinformatics analyses of highly heterogeneous cancer cells, combined with tumor "omics" profiles, can optimally characterize the expression patterns and activity of specific tumor biomarkers. Subsequent in vitro and in vivo validation, of specific disease biomarkers (using multiple methodologies), can improve prediction of patient stratification according to drug response or nonresponse.

Ligularia fischeri inhibits endothelial cell proliferation, invasion and tube formation through the inactivation of mitogenic signaling pathways and regulation of vascular endothelial cadherin distribution and matrix metalloproteinase expression.

Ligularia fischeri (LF) has been used as an edible herb and traditional medicine for the treatment of inflammatory and infectious diseases. In the present study, we report the effects and molecular mechanism of the ethanolic extract of LF on cell proliferation, invasion and tube formation in human umbilical vein endothelial cells (HUVECs). LF-mediated inhibition of cell proliferation was accompanied by reduced expression of cell cycle-related proteins such as cyclin-dependent kinases (Cdks) and cyclins, leading to pRb hypophosphorylation and G1 phase cell cycle arrest. We also show that LF treatment inhibited cell invasion and tube formation in HUVECs. These anti-angiogenic activities of LF were associated with the inactivation of mitogenic signaling pathways, induction of vascular endothelial (VE)-cadherin distribution at cell-cell contacts and inhibition of matrix metalloproteinase (MMP) expression. Collectively, our findings demonstrate the pharmacological functions and molecular mechanisms of LF in regulating endothelial cell fates, and support further development as a potential therapeutic agent for the treatment and prevention of angiogenesis-related disorders including cancer.

Kazinol-P from Broussonetia kazinoki enhances skeletal muscle differentiation via p38MAPK and MyoD.

The activation of MyoD family transcription factors is critical for myogenic differentiation, which is fundamental to the regeneration of skeletal muscle after injury. Kazinol-P (KP) from Broussonetia kazinoki (B. kazinoki), a natural compound, has been reported to possess an anti-oxidant function. In a screen of natural compounds for agonists of the MyoD activity, we identified KP and examined its effect on myoblast differentiation. Consistently, KP enhanced the myotube formation, accompanied with upregulation of myogenic markers such as MHC, Myogenin and Troponin-T. KP treatment in C2C12 myoblasts led to strong activation of a key promyogenic kinase p38MAPK in a dose, and time-dependent manner. Furthermore, KP treatment enhanced the MyoD-mediated trans-differentiation of 10T1/2 fibroblasts into myoblasts. Taken together, KP promotes myogenic differentiation through activation of p38MAPK and MyoD transcription activities. Thus KP may be a potential therapeutic candidate to prevent fibrosis and improve muscle regeneration and repair.

Broussonetia kazinoki modulates the expression of VEGFR-2 and MMP-2 through the inhibition of ERK, Akt and p70S6K­dependent signaling pathways: Its implication in endothelial cell proliferation, migration and tubular formation.

Broussonetia kazinoki (BK) has been used as a traditional medicine to improve vision, as well as for inflammatory and infectious diseases. In the present study, we investigated the effects and molecular mechanism of the ethanolic extract of BK on cell proliferation, migration and tubular formation in vascular endothelial growth factor-A (VEGF-A)-treated human umbilical vein endothelial cells. BK treatment inhibited VEGF-A-stimulated endothelial cell proliferation through the downregulation of cell cycle-related proteins including cyclin-dependent kinases and cyclins. Moreover, BK treatment suppressed cell migration and tubular formation in response to VEGF-A. These anti-angiogenic activities of BK were associated with the inactivation of mitogenic signaling pathways including extracellular signal-regulated kinase, Akt and p70S6K, and the subsequent downregulation of VEGFR-2 and matrix metalloproteinase-2. Taken together, these findings suggest further evaluation and development of BK as a potential therapeutic agent for the treatment and prevention of angiogenesis-related diseases including cancer.

Cyanidin-3-O-sambubioside from Acanthopanax sessiliflorus fruit inhibits metastasis by downregulating MMP-9 in breast cancer cells MDA-MB-231.

Anthocyanins play an important role in physiological functions related to human health. This study aimed to investigate the inhibitory effect of cyanidin-3-O-sambubioside isolated from Acanthopanax sessiliflorus fruit on cancer cell metastasis. The inhibitory effect of cyanidin-3-O-sambubioside on angiogenesis was assessed by chorioallantoic membrane and tube formation assays. Cyanidin-3-O-sambubioside interrupted the formation of neovasculature and tube-like structures in a dose-dependent manner. It inhibited the wound healing migration and invasion of MDA-MB-231 cells through reconstituted extracellular matrix (Matrigel). Gelatin zymography revealed that cyanidin-3-O-sambubioside significantly decreased the secretion of matrix metalloproteinase-9 and inhibited matrix metalloproteinase-9 expression. In additional, cyanidin-3-O-sambubioside exerted an inhibitory effect on Akt phosphorylation. These results suggest that cyanidin-3-O-sambubioside inhibits metastasis processes, such as angiogenesis and invasion, in breast cancer cells through regulation of matrix metalloproteinase-9 activity.

Safety evaluation of stamp type digital microneedle devices in hairless mice.

BACKGROUND: Microneedles provide a minimally invasive means to transport molecules into the skin. A number of specific strategies have been employed to use microneedles for transdermal delivery. OBJECTIVE: The purpose of this study was to investigate the safety of two new digital microneedle devices (Digital Hand® and Digital Pro®; Bomtech Electronics Co., Ltd., Seoul, Korea) for the perforation of skin in skin-hairless-1 mice. This device replaces conventional needles and is designed specifically for intradermal delivery. METHODS: We used two newly developed digital microneedle devices to perforate the skin of skin-hairless-1 mice. We conducted a comparative study of the two digital microneedle devices and DTS® (Disk type-microneedle Therapy System; DTS lab., Seoul, Korea). To evaluate skin stability, we performed visual and dermatoscopic inspections, measurements of transepidermal water loss, and biopsies. RESULTS: The two novel digital microneedle devices did not induce significant abnormalities of the skin on visual or dermatoscopic inspection, regardless of needle size (0.25~2.0 mm). No significant histopathological changes, such as inflammatory cell infiltration, desquamation of the stratum corneum, or disruption of the basal layer, were observed. The digital microneedle devices and microneedle therapy system produced similar results on measures of skin stability. CONCLUSION: These two novel digital microneedle devices are safe transdermal drug delivery systems.

Changes in bone mineral density in postmenopausal women treated with epidural steroid injections for lower back pain.

BACKGROUND: Therapy with corticosteroids often results in bone loss and corticosteroid-induced osteoporosis. In previous studies, bone mineral density (BMD) has been examined after administration of relatively high oral doses of corticosteroids. However, practitioners use comparatively lower doses of corticosteroids for epidural steroid injections (ESI). The interactions and relationships between BMD and ESI remain to be determined. OBJECTIVE: The aim of this study was to explore the relationship between BMD and ESI in postmenopausal women treated for lower back pain. STUDY DESIGN: This study was a retrospective evaluation. METHODS: We reviewed the medical records of postmenopausal women with lower back pain who were treated with or without ESI. BMD was measured before treatment and one year after treatment in the lumbar spine, femoral neck, and total femur. A total of 90 postmenopausal women were divided into 2 groups. Group 1 patients received medications without ESI; Group 2 patients received ESI more than 4 times, with a cumulative administered triamcinolone dose of > 120 mg. RESULTS: Decreased BMD was observed in patients treated with ESI. However, no significant difference was observed between or within the groups in terms of mean percentage change from baseline BMD. LIMITATIONS: First, this study is limited by the fact that it was retrospective. Second, our study did not consider the use of ESI with high-dose corticosteroids. Third, our study did not include any long-term assessments of the effects of ESI on BMD. CONCLUSIONS: These data suggest that ESI using triamcinolone (over 200 mg) for a period of one year will have a negative effect on BMD in postmenopausal women treated for lower back pain. However, ESI therapy using a maximum cumulative triamcinolone dose of 200 mg in one year would be a safe treatment method with no significant impact on BMD.

Bilayered constructs aimed at osteochondral strategies: the influence of medium supplements in the osteogenic and chondrogenic differentiation of amniotic fluid-derived stem cells.

The development of osteochondral tissue engineered interfaces would be a novel treatment for traumatic injuries and aging associated diseases that affect joints. This study reports the development of a bilayered scaffold, which consists of both bone and cartilage regions. On the other hand, amniotic fluid-derived stem cells (AFSCs) could be differentiated into either osteogenic or chondrogenic cells, respectively. In this study we have developed a bilayered scaffolding system, which includes a starch/polycaprolactone (SPCL) scaffold for osteogenesis and an agarose hydrogel for chondrogenesis. AFSC-seeded scaffolds were cultured for 1 or 2 weeks in an osteochondral-defined culture medium containing both osteogenic and chondrogenic differentiation factors. Additionally, the effect of the presence or absence of insulin-like growth factor-1 (IGF-1) in the culture medium was assessed. Cell viability and phenotypic expression were assessed within the constructs in order to determine the influence of the osteochondral differentiation medium. The results indicated that, after osteogenic differentiation, AFSCs that had been seeded onto SPCL scaffolds did not require osteochondral medium to maintain their phenotype, and they produced a protein-rich, mineralized extracellular matrix (ECM) for up to 2 weeks. However, AFSCs differentiated into chondrocyte-like cells appeared to require osteochondral medium, but not IGF-1, to synthesize ECM proteins and maintain the chondrogenic phenotype. Thus, although IGF-1 was not essential for creating osteochondral constructs with AFSCs in this study, the osteochondral supplements used appear to be important to generate cartilage in long-term tissue engineering approaches for osteochondral interfaces. In addition, constructs generated from agarose-SPCL bilayered scaffolds containing pre-differentiated AFSCs may be useful for potential applications in regeneration strategies for damaged or diseased joints.

Inhibition of cytokine expression by a butanol extract from Cordyceps bassiana.

Cordyceps species have been known since long as a multi-utility ethnomedicinal herbal in Korea, China and Japan. It has been reported to exhibit a number of properties such as anti-oxidative, anti-cancer, antiinflammatory, anti-diabetic, and anti-obesity effects. In a previously conducted study, we had demonstrated that the ethanol extract of Cordyceps bassiana was able to suppress the production of interleukin (IL)-12 and interferon (IFN)-gamma in macrophages and T lymphocytes. In this study, we were able to further explore the molecular basis of its inhibitory mechanism using a butanol fraction of this herbal (Cb-BF) preparation. Similarly, this fraction also blocked the expression of cytokines such as IL-12 and tumor necrosis factor (TNF)-alpha as well as the proliferation of splenic lymphocytes and their production of IFN-gamma but not IL-4. Cb-BF suppressed the luciferase activities that are mediated by nuclear factor (NF)-kappaB, activator protein (AP)-1, and signal transducers and activators of transcription (STAT)-1. In agreement with this, these fractions diminished the translocation of the transcription factors into the nucleus. The study also demonstrated that the upstream signaling events for the activation of these factors such as spleen tyrosine kinase (Syk), janus kinase (JAK)-2, and extracellular signal-regulated kinase (ERK) were suppressed. Therefore, these results suggest that the butanol extract of Cordyceps bassiana may contain more than one active component capable of inhibiting the inflammatory signaling cascade and this can be considered as a potential candidate for treatment of diseases that require suppression of immune system.

Effects of audio tone guidance on performance of CPR in simulated cardiac arrest with an advanced airway.

THE AIM OF THE STUDY: Despite the emphasis of cardiopulmonary resuscitation (CPR) quality, the performance of on-site CPR is reported to be frequently unsuccessful. In order to improve CPR quality, various feedback systems have been developed, but they have not yet been widely used on site due to low economic efficiency. The present study was attempted to determine whether CPR quality can be improved using audio tone guidance. THE METHODS: A total of 80 seniors at our medical school and college of nursing participated in the study. After they were trained in CPR according to the 2005 guidelines, they performed CPR using a cardiac arrest model with an advanced airway. The participants were organized into 40 groups. After they took Test 1 without any feedback for 2 min, they were randomly assigned to the feedback and control groups and took Test 2 for 2 min. In the feedback group, a low-pitched sound was delivered every 0.6 s for the guidance of chest compression and a high-pitched sound was simultaneously delivered every 10 deliveries of a low-pitched sound for the guidance of ventilation at 6s intervals. THE RESULTS: In the feedback group the mean compression rate significantly improved in accuracy from 111.5+/-13.7/min to 100.1+/-3.2/min (P<0.01), and ventilation counts significantly improved in accuracy from 7.4+/-1.8/min to 9.9+/-0.3/min (P<0.01). However, the mean compression depth significantly decreased from 39.3+/-9.5 mm to 35.8+/-8.2 mm (P<0.01). THE CONCLUSION: Audio tone guidance ensures better chest compression rate and ventilation rate but this does not necessarily result in a better CPR quality.