The anti-angiogenic herbal composition Ob-X inhibits adipose tissue growth in obese mice

Objective: The growth and development of adipose tissue are thought to be associated with angiogenesis and extracellular matrix remodeling. Since the composition of the herbal extract called Ob-X has been shown to have both anti-angiogenic and matrix metalloproteinase (MMP)-inhibiting activities, we hypothesized that growth of adipose tissue can be regulated by Ob-X. Materials and Methods: The effects of Ob-X on angiogenesis and extracellular matrix remodeling were measured using in vitro and ex vivo assays. The effects of Ob-X on adipose tissue growth were investigated with nutritionally obese mice. Results: Ob-X inhibited angiogenesis in a dose-dependent manner in the human umbilical vein endothelial cell (HUVEC) tube formation assay in vitro and the rat aortic ring assay ex vivo. Ob-X also suppressed MMP activity in vitro. Administration of Ob-X to high fat diet-induced obese mice produced significant reductions in body weight gain and adipose tissue mass, compared to controls. The mass of both subcutaneous (SC) and visceral (VSC) fat was reduced in Ob-X-treated mice. The size of adipocytes in SC and VSC adipose tissues was also significantly reduced in Ob-X-treated mice. Ob-X treatment decreased the blood vessel density and MMP activity in VSC adipose tissues of nutritionally obese mice. Ob-X reduced mRNA levels of angiogenic factors (VEGF-A and FGF-2) and MMPs (MMP-2 and MMP-9), whereas it increased mRNA levels of angiogenesis inhibitors (TSP-1 and TIMP-2) in SC and VSC adipose tissues of nutritionally obese mice. Conclusion: Ob-X, which has anti-angiogenic and MMP-inhibitory activities, reduces adipose tissue mass in nutritionally induced obese mice, providing evidence that adipose tissue growth and development may be prevented by inhibiting angiogenesis. In addition, these data suggest that regulation of adipose tissue growth by inhibiting angiogenesis may alter the expression of genes involved in angiogenesis and the MMP system

Cognitive and Emotional Aspects of Cupping Therapy

Cupping therapy has recently gained public attention and is widely used in many regions. Some patients are resistant to being treated with cupping therapy, as visually unpleasant marks on the skin may elicit negative reactions. This study aimed to identify the cognitive and emotional components of cupping therapy. Twenty-five healthy volunteers were presented with emotionally evocative visual stimuli representing fear, disgust, happiness, neutral emotion, and cupping, along with control images. Participants evaluated the valence and arousal level of each stimulus. Before the experiment, they completed the Fear of Pain Questionnaire-III. In two-dimensional affective space, emotional arousal increases as hedonic valence ratings become increasingly pleasant or unpleasant. Cupping therapy images were more unpleasant and more arousing than the control images. Cluster analysis showed that the response to cupping therapy images had emotional characteristics similar to those for fear images. Individuals with a greater fear of pain rated cupping therapy images as more unpleasant and more arousing. Psychophysical analysis showed that individuals experienced unpleasant and aroused emotional states in response to the cupping therapy images. Our findings suggest that cupping therapy might be associated with unpleasant-defensive motivation and motivational activation. Determining the emotional components of cupping therapy would help clinicians and researchers to understand the intrinsic effects of cupping therapy

Amelioration of muscle wasting by glucagon‐like peptide‐1 receptor agonist in muscle atrophy

Abstract Background Skeletal muscle atrophy is defined as a reduction of muscle mass caused by excessive protein degradation. However, the development of therapeutic interventions is still in an early stage. Although glucagon‐like peptide‐1 receptor (GLP‐1R) agonists, such as exendin‐4 (Ex‐4) and dulaglutide, are widely used for the treatment of diabetes, their effects on muscle pathology are unknown. In this study, we investigated the therapeutic potential of GLP‐1R agonist for muscle wasting and the mechanisms involved. Methods Mouse C2C12 myotubes were used to evaluate the in vitro effects of Ex‐4 in the presence or absence of dexamethasone (Dex) on the regulation of the expression of muscle atrophic factors and the underlying mechanisms using various pharmacological inhibitors. In addition, we investigated the in vivo therapeutic effect of Ex‐4 in a Dex‐induced mouse muscle atrophy model (20 mg/kg/day i.p.) followed by injection of Ex‐4 (100 ng/day i.p.) for 12 days and chronic kidney disease (CKD)‐induced muscle atrophy model. Furthermore, we evaluated the effect of a long‐acting GLP‐1R agonist by treatment of dulaglutide (1 mg/kg/week s.c.) for 3 weeks, in DBA/2J‐mdx mice, a Duchenne muscular dystrophy model. Results Ex‐4 suppressed the expression of myostatin (MSTN) and muscle atrophic factors such as F‐box only protein 32 (atrogin‐1) and muscle RING‐finger protein‐1 (MuRF‐1) in Dex‐treated C2C12 myotubes. The suppression effect was via protein kinase A and protein kinase B signalling pathways through GLP‐1R. In addition, Ex‐4 treatment inhibited glucocorticoid receptor (GR) translocation by up‐regulating the proteins of GR inhibitory complexes. In a Dex‐induced muscle atrophy model, Ex‐4 ameliorated muscle atrophy by suppressing muscle atrophic factors and enhancing myogenic factors (MyoG and MyoD), leading to increased muscle mass and function. In the CKD muscle atrophy model, Ex‐4 also increased muscle mass, myofiber size, and muscle function. In addition, treatment with a long‐acting GLP‐1R agonist, dulaglutide, recovered muscle mass and function in DBA/2J‐mdx mice. Conclusions GLP‐1R agonists ameliorate muscle wasting by suppressing MSTN and muscle atrophic factors and enhancing myogenic factors through GLP‐1R‐mediated signalling pathways. These novel findings suggest that activating GLP‐1R signalling may be useful for the treatment of atrophy‐related muscular diseases

VanB-vanA Incongruent VRE Isolated from Animals and Humans in 1999

16 chicken isolates and four clinical isolates of VanB-vanA incongruent vancomycinresistant Enterococcus faecium strains without vanS were isolated in 1999. Pulsed-field gel electrophoresis revealed only a peripheral relationship between the chicken isolates and clinical isolates, but suggested clonal spread in the chicken isolates.This work was supported by the Technology Development Program for Agriculture and Forestry, Ministry of Agriculture and Forestry (Grant No. 201102-3) and by a grant from the Korea Health 21 R&D Project, Ministry of Health and Welfare, Republic of Korea (03-PJ1-PG1-CH03-0002)

Commonality and Specificity of Acupuncture Point Selections

Objective. Because individual acupoints have a wide variety of indications, it is difficult to accurately identify the associations between acupoints and specific diseases. Thus, the present study aimed at revealing the commonality and specificity of acupoint selections using virtual medical diagnoses based on several cases. Methods. Eighty currently practicing Korean Medicine doctors were asked to prescribe acupoints for virtual acupuncture treatment after being presented with medical information extracted from 10 case reports. The acupoints prescribed for each case were quantified; the data were normalised and compared among the 10 cases using z-scores. A hierarchical cluster analysis was conducted to categorise diseases treated based on the acupoint prescription patterns. Additionally, network analyses were performed on the acupoint prescriptions, at the individual case and cluster level. Results. Acupoints ST36, LI4, and LR3 were most commonly prescribed across all diseases. Regarding the specific acupoints prescribed in each cluster, acupoints around the disease site (knee and lower back) were frequently used in cluster A (musculoskeletal symptoms), acupoints LI4, LR3, PC6, and KI3 were frequently used in cluster B (psychiatric symptoms), and acupoints ST36, LI4, LR3, PC6, CV12, and SP6 were frequently used in cluster C (several symptoms of diseases of internal medicine). Conclusions. The present study identified the commonality and specificity of acupoint selections based on virtual acupuncture treatments prescribed by practicing clinicians. Acupoint selection patterns, which were defined using a top-down approach in previous studies and classical medical texts, may be further elucidated using a bottom-up approach based on patient medical records

The effects of luteinising hormone gene polymorphism on the outcomes of in vitro fertilisation and embryo transfer

Trp8Arg polymorphism of the LH beta gene has decreased bioactivity in vivo and previous studies showed conflicting data on the effect of LH beta gene polymorphism on the IVF outcome. In this study, 591 IVF patients were recruited. Patients with the variant allele(s) were the carrier group. In GnRH antagonist cycles, the clinical pregnancy rate was significantly lower in the carrier group (18.9%) than in the noncarrier group (37.1%). In long GnRH agonist cycles, the clinical pregnancy rate was comparable between both groups. To clarify the effect of COH protocols, IVF outcomes in the GnRH antagonist and long GnRH agonist protocol groups in carriers were analysed. Among carriers, the clinical pregnancy rate was significantly lower in the GnRH antagonist protocol group (18.9%) than in the long GnRH agonist protocol group (45.2%). Single nucleotide polymorphism analysis may contribute to the individualisation of COH protocols for each patient in the future.Impact Statement What is already known on this subject? Trp8Arg polymorphism of the LH beta gene is known to have decreased bioactivity in vivo. Previous studies have demonstrated hypo-sensitivity in the patients with the variant LH beta protein, while other study showed similar carrier frequency between the poor and the normal response group. What the results of this study add? The variant LH beta gene was associated with a lower clinical pregnancy rate in GnRH antagonist cycles but not in long GnRH agonist cycles. What the implications are of these findings for clinical practice and/or further research? Single nucleotide polymorphism analysis may contribute to the individualisation of COH protocols for each patient in the future

Electrical Impedance Monitoring of C2C12 Myoblast Differentiation on an Indium Tin Oxide Electrode

Electrical cell-substrate impedance sensing is increasingly being used for label-free and real-time monitoring of changes in cell morphology and number during cell growth, drug screening, and differentiation. In this study, we evaluated the feasibility of using ECIS to monitor C2C12 myoblast differentiation using a fabricated indium tin oxide (ITO) electrode-based chip. C2C12 myoblast differentiation on the ITO electrode was validated based on decreases in the mRNA level of MyoD and increases in the mRNA levels of myogenin and myosin heavy chain (MHC). Additionally, MHC expression and morphological changes in myoblasts differentiated on the ITO electrode were comparable to those in cells in the control culture dish. From the monitoring the integration of the resistance change at 21.5 kHz, the cell differentiation was label-free and real-time detectable in 30 h of differentiation (p < 0.05)

Preface for the Proceedings of SIMS XIX, Jeju, Korea 2013

FALS

Chemokine (C-C Motif) Ligand 8 and Tubulo-Interstitial Injury in Chronic Kidney Disease

Kidney fibrosis has been accepted to be a common pathological outcome of chronic kidney disease (CKD). We aimed to examine serum levels and tissue expression of chemokine (C-C motif) ligand 8 (CCL8) in patients with CKD and to investigate their association with kidney fibrosis in CKD model. Serum levels and tissue expression of CCL8 significantly increased with advancing CKD stage, proteinuria level, and pathologic deterioration. In Western blot analysis of primary cultured human tubular epithelial cells after induction of fibrosis with rTGF-β, CCL8 was upregulated by rTGF-β treatment and the simultaneous treatment with anti-CCL8 mAb mitigated the rTGF-β-induced an increase in fibronectin and a decrease E-cadherin and BCL-2 protein levels. The antiapoptotic effect of the anti-CCL8 mAb was also demonstrated by Annexin V/propidium iodide staining assay. In qRT-PCR analysis, mRNA expression levels of the markers for fibrosis and apoptosis showed similar expression patterns to those observed by western blotting. The immunohistochemical analysis revealed CCL8 and fibrosis- and apoptosis-related markers significantly increased in the unilateral ureteral obstruction model, which agrees with our in vitro findings. In conclusion, CCL8 pathway is associated with increased risk of kidney fibrosis and that CCL8 blockade can ameliorate kidney fibrosis and apoptosis