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Background Skeletal muscle atrophy is a severe condition that involves loss of muscle mass and quality. Drug intake can also cause muscle atrophy. Biguanide metformin is the first‐line and most widely prescribed anti‐diabetic drug for patients with type 2 diabetes. The molecular mechanism of metformin in muscle is unclear. Methods Myostatin expression was investigated at the protein and transcript levels after metformin administration. To investigate the pathways associated with myostatin signalling, we used real‐time polymerase chain reaction, immunoblotting, luciferase assay, chromatin immunoprecipitation assay, co‐immunoprecipitation, immunofluorescence, primary culture, and confocal microscopy. Serum analysis, physical performance, and immunohistochemistry were performed using our in vivo model. Results Metformin induced the expression of myostatin, a key molecule that regulates muscle volume and triggers the phosphorylation of AMPK. AMPK alpha2 knockdown in the background of metformin treatment reduced the myostatin expression of C2C12 myotubes (−49.86 ± 12.03%, P 3.12‐fold ± 0.13, P 3.3‐fold, P

BACKGROUND: The excimer laser/light (EL) has been reported to be effective for alopecia areata (AA), but its treatment response has not been systematically reviewed. OBJECTIVE: To determine the treatment reponse and safety of EL treatment of AA. METHODS: A comprehensive search of the Medline, EMBASE, Cochrane library, and Web of Science (from inception to December 31, 2018) was conducted to identify prospective clinical studies assessing the treatment response of EL for AA. The primary outcome was cosmetically acceptable hair regrowth (hair regrowth ≥75%); random-effects meta-analyses using generic inverse variance weighting were performed to estimate treatment responses. The study was registered with PROSPERO (CRD42019121092). RESULTS: Of 52 records initially identified, 13 full-text articles were finally assessed in terms of eligibility. A total of 9 prospective clinical studies (129 AA patients) including 5 controlled clinical trials were identified. Cosmetically acceptable hair regrowth was achieved in 50.2% (95% confidence interval 31.5%-68.9%; 8 studies). EL treatment significantly improved hair regrowth compared to untreated controls (relative risk 7.83; 95% confidence interval 2.11-29.11; 5 controlled clinical trials). No serious adverse effect was noted. CONCLUSIONS: EL treatment appeared to produce a favorable therapeutic response in AA patients. The use of EL should be encouraged for AA patients with the advantages of the non-invasiveness and no systemic effect.

Micropigmentation, also termed medical tattooing, can be a useful alternative treatment for patients with vitiligo who are resistant to conventional treatments. To assess the benefits and risks of micropigmentation in the treatment of refractory vitiligo, 25 lesions of 14 patients with vitiligo (Fitzpatrick skin types III and IV) were subjected to micropigmentation using an electric tattooing machine between December 2018 and March 2019. The procedure was repeated until satisfactory results were obtained. Treatment response was assessed by color matching of the treated lesion and surrounding skin using a 4-point scale (poor, fair, good and excellent). Excellent color matching was achieved in 80% (20/25) of cases after a median of three (range, 1-5) treatment sessions. Procedure-associated pain was considerable, but no anesthetic injection was needed. Immediate erythema and swelling were noticed after each procedure, but resolved within a few days. Overall, the treatment was tolerable. This study was limited by a small sample, no control group and a short follow-up period. This study revealed that micropigmentation was beneficial for patients with refractory vitiligo who had light to moderately colored skin. Pigment selection, implantation depth and selection of body parts amenable to treatment were critical.

BACKGROUND The prevalence of hidradenitis suppurativa (HS) in Asia is unknown. The associations between HS and other autoimmune disorders have rarely been reported. OBJECTIVE We sought to determine the prevalence of and diseases associated with HS using the National Health Insurance (NHI) database. METHODS We examined Korean NHI claim database data from 2007 to 2016. We enrolled all patients with HS and age- and sex-matched control subjects without HS. We estimated the period prevalence of HS and associated comorbidities in Korea. RESULTS We identified 28 516 patients with HS (61.3% males and 38.7% females). The period prevalence rate was 0.06%, 55.8 patients (95% confidence interval 55.1-56.4) per 100 000 persons, and the female-to-male ratio was 1 : 1.6. HS patients were at significantly increased risk of rheumatoid arthritis, ankylosing spondylitis, type 1 diabetes, ulcerative colitis, type 2 diabetes, hypertension, hyperlipidaemia, acne conglobata, pilonidal cysts, psoriasis, pyoderma gangrenosum, alopecia areata and vitiligo. CONCLUSION The overall prevalence of HS in Korea was lower than that in Western populations, and male patients predominated.

Background Although topical retinoic acid effectively restores photoaged skin, the associated irritation limits the utility of the material. Retinaldehyde (RAL) is the natural precursor of retinoic acid and can also be used to treat photoaged skin; the safety profile is good. Aims To evaluate the efficacy and safety of new anti-aging creams containing RAL at 0.1% and 0.05% used to treat photoaged skin. Patients and methods We enrolled 40 female Korean volunteers who applied RAL 0.1% or RAL 0.05% creams twice daily for 3 months. Wrinkles on, and the textures of, both crow's feet were quantitatively assessed using the Antera 3D® system. Transepidermal water loss (TEWL), skin hydration, the melanin index, and skin brightness were also evaluated. Overall improvement was assessed using a five-point scale by both the patients and the dermatologists. Results The 3-month application improved overall photoaging in both RAL 0.1% (95%) and RAL 0.05% groups (95%). Both RAL 0.1% and RAL 0.05% afforded significant textural improvements (13.7% and 12.6%, respectively), reduced the TEWL (14.5%, 17.9%), and increased hydration (10.2%, 6.0%); however, no statistical differences were observed between two groups. Only RAL 0.1% significantly improved the melanin index (by 6.5%). Conclusions Both RAL 0.1% and RAL 0.05% creams were well tolerated and improved skin hydration and texture. However, only RAL 0.1% cream improved the melanin index.

Objectives Emerging oncotherapeutic strategies require the induction of an immunostimulatory tumor microenvironment (TME) containing numerous tumor‐reactive CD8+ T cells. Interleukin‐7 (IL‐7), a T‐cell homeostatic cytokine, induces an antitumor response; however, the detailed mechanisms underlying the contributions of the IL‐7 to TME remain unclear. Here, we aimed to investigate the mechanism underlying the induction of antitumor response by hybrid Fc‐fused long‐acting recombinant human IL‐7 (rhIL‐7‐hyFc) through regulation of both adaptive and innate immune cells in the TME. Methods We evaluated rhIL‐7‐hyFc‐mediated antitumor responses in murine syngeneic tumor models. We analysed the cellular and molecular features of tumor‐infiltrating lymphocytes (TILs) and changes in the TME after rhIL‐7‐hyFc treatment. Furthermore, we evaluated the antitumor efficacy of rhIL‐7‐hyFc combined with chemotherapy and checkpoint inhibitors (CPIs). Results Systemic delivery of rhIL‐7‐hyFc induced significant therapeutic benefits by expanding CD8+ T cells with enhanced tumor tropism. In tumors, rhIL‐7‐hyFc increased both tumor‐reactive and bystander CD8+ TILs, all of which displayed enhanced effector functions but less exhausted phenotypes. Moreover, rhIL‐7‐hyFc suppressed the generation of immunosuppressive myeloid cells in the bone marrow of tumor‐bearing mice, resulting in the immunostimulatory TME. Combination therapy with chemotherapy and CPIs, rhIL‐7‐hyFc elicited a strong antitumor response and even under a T lymphopenic condition by restoring CD8+ T cells. When combined with chemotherapy and CPIs, rhIL‐7‐hyFc administration enhanced antitumor response under intact andlymphopenic conditions by restoring CD8+ T cells. Conclusion Taken together, these data demonstrate that rhIL‐7‐hyFc induces antitumor responses by generating T‐cell‐inflamed TME and provide a preclinical proof of concept of immunotherapy with rhIL‐7‐hyFc to enhance therapeutic responses in the clinic., In this study, we found that a systemic administration of a hybrid Fc‐fused long‐acting recombinant human IL‐7 (rhIL‐7‐hyFc) induces antitumor activity by promoting an inflamed tumor microenvironment. rhIL‐7‐hyFc significantly augments CD8+ T‐cell responses while inhibiting the accumulation of immunosuppressive cells in tumors. This finding suggests that rhIL‐7‐hyFc can be a potential new cytokine‐based agent for cancer immunotherapy.

Background Detection of Helicobacter pylori in gastric biopsy is important for appropriate treatment and prevention of gastric carcinoma and lymphoma. A novel peptide nucleic acid probe (PNA)-based real-time polymerase chain reaction (PCR) method was developed for detection of H pylori and A2142G/A2143G mutation of the 23S rRNA gene, which is associated with clarithromycin resistance. Methods To evaluate the performance of the PNA probe-based PCR method, a total of 409 gastric biopsy samples were analyzed by PNA probe-based PCR and compared with other H pylori detection methods, including hematoxylin and eosin (HE) and Warthin-Starry (WS) staining, immunohistochemistry (IHC). A2142G/A2143G mutation of the 23S rRNA gene was tested by dual priming oligonucleotide (DPO)-based PCR and Sanger sequencing to evaluate PNA probe-based PCR. Results Among 271 cases that were positive for H pylori on IHC which was considered as a standard method, 264 cases (97.4%) and 259 cases (95.6%) were positively detected by HE/WS and PNA probe-based qPCR, respectively. Of 100 H pylori-positive patients tested by IHC, H pylori was detected in 93 cases (93.0%) by PNA probe-based PCR, 86 cases (86.0%) by DPO-based PCR, and 93 cases (93.0%) by conventional PCR. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of PNA probe-based qPCR were 93.0%, 94.9%, 93.9%, 94.9%, and 93.0%, respectively, which were all higher than those of DPO-based PCR. When Sanger sequencing was determined as a standard method to detect A2142G/A2143G mutations, the sensitivity of the PNA- and DPO-based methods was 100% and 94.4%, respectively, and the specificity was 100% for both methods. Conclusion PNA probe-based qPCR is an appropriate method for detecting H pylori and the clarithromycin resistance-associated mutation type.

Objectives To test the utility of a memory-encoding strategy for improving prospective memory (PM), the ability to remember to execute future goals (e.g., remembering to take medications), which plays an important role in independent living in healthy older adults and those with very mild Alzheimer's disease (AD). Design Participants were randomly assigned to an encoding strategy condition or a standard encoding condition. Setting A longitudinal study conducted at an Alzheimer's disease research center. Testing took place at the center and in a university testing room. Participants Healthy older adults (Clinical Dementia Rating (CDR) = 0.0, n = 38) and those classified as being in the very mild stage of AD (CDR = 0.5, n = 34). Intervention A simple strategy (“If I see Cue X, then I will perform Intention Y”) was used to strengthen PM encoding and reduce the probability of forgetting to execute one's future plans. Measurements PM was assessed using Virtual Week, a laboratory task that requires the simulation of common PM tasks (the types of tasks performed in everyday life), such as taking one's medication at breakfast. Results The encoding strategy significantly reduced PM failures in healthy older adults and those with very mild AD and was effective regardless of the individual's episodic memory ability. Conclusion This encoding strategy was successful in reducing PM errors in healthy older adults and those with mild AD with a range of memory abilities.

Aim Although previous reports have addressed worry and rumination as prominent cognitive processes in generalized anxiety disorder (GAD) and major depressive disorder (MDD) and their distinct correlation with anxious and depressive symptoms, the differential association of worry and rumination with the diagnosis of GAD and MDD remains unclear. The purpose of this study was to investigate the distinct features of worry and rumination in factor structure and their predictive validity for the diagnosis of GAD and MDD. Methods Four hundred and sixty-eight patients with GAD (n = 148) and MDD (n = 320) were enrolled and the diagnoses were confirmed with the Structured Clinical Interview for DSM-IV. Participants completed the Penn State Worry Questionnaire and Ruminative Response Scale and the severity of anxiety and depressive symptoms was assessed via clinician ratings. Results In joint factor analysis using the Penn State Worry Questionnaire and Ruminative Response Scale items, worry and rumination emerged as distinct factors. In logistic regression analyses, worry contributed to a higher probability of the diagnosis of GAD than rumination, as rumination did in MDD than worry. Conclusion This is the first comprehensive study investigating the diagnostic utility of worry and rumination in a well-defined clinical sample of both GAD and MDD. Our results suggest that worry and rumination are distinct cognitive processes and play a differential role in the diagnosis of GAD and MDD, distinguishing them at the cognitive level.

cope Previous reports suggest that licorice extract has various metabolically beneficial effects and may help to alleviate adiposity and hyperlipidemia. However, underlying anti-obesity mechanisms still remain elusive. Moreover, it is unknown which single ingredient in licorice extract would mediate such effects. We aimed to demonstrate that licorice extract and its active ingredients can inhibit adipocyte differentiation and fat accumulation. Methods and results 18β-glycyrrhetinic acid (18β-GA) alleviated the effects of CB1R agonist, anandamide (AEA) on CB1R signaling in a concentration-dependent manner. Consistently, 18β-GA suppressed AEA-induced adipocyte differentiation in 3T3-L1 cells through the downregulation of AEA-induced MAPK activation and expression of adipogenic genes including C/EBP-α and PPAR-γ. The protein levels of fatty acid synthase and stearoyl-CoA desaturase 1 were also decreased and the phosphorylation of acetyl-CoA carboxylase was increased in 18β-GA pretreated cells. The supplementation of 18β-GA significantly lowered body weight, fat weight, and plasma lipids levels in obese animal models. Conclusion These results may provide a novel insight into the molecular mechanism involved in anti-adipogenic and anti-obesity effects of 18β-GA by suppressing the activation of CB1R induced by AEA. Thus, 18β-GA may exert beneficial effects against obesity-related metabolic disorders.

Meju, a naturally fermented soy block used to produce soy paste and soy sauce in Korea, is suggested to exhibit hypolipidemic and antiinflammatory activities; however, its mechanisms of action are elusive. Here, we report that the water-soluble fibers but not the amino acids and peptides from meju exhibited hypolipidemic activity in vivo. Feeding of fermented soybean fibers (FSF) from meju reduced plasma cholesterol, triglyceride, adipocyte size, and hepatic lipid accumulation in C57BL/6J mice. FSF treatment reduced HMG-CoA reductase expression, whereas the expression of genes in the fatty acid uptake and subsequent beta-oxidation were significantly induced in the livers. Hepatic lipogenic genes, including Srebp1c and Lxrα, were unaltered. Feeding with the fermented soybean peptides and amino acids (FSPA) induced the expression of lipogenic genes, which may have canceled the induction of low-density lipoprotein receptor and Cyp7a1 gene expressions in FSPA livers. The plasma concentrations of C-reactive protein, TNF-α,andinterlukin-6weresignificantlyreducedintheFSF, FSPA,andmejugroups compared with the control groups, suggesting that both of the fibers and peptides/amino acids from meju may be beneficial. These findings suggest that soluble fibers from meju are critical hypolipidemic components that regulate hepatic gene expressions and reduce proinflammatory cytokinesin vivo. Copyright © 2014 John Wiley & Sons, Ltd.

c ) Intelligent Synthetic Biology Center, KAIST, Daejeon 305-701, Korea Two new bisabolane sesquiterpenoids, 1 and 2, along with five known ones, 13-hydroxyxanthorrhizol (3), 12,13-epoxyxanthorrhizol (4), xanthorrhizol (5), b-curcumene (6), and b-bisabolol (7), were isolated from the rhizomes of Curcuma xanthorrhiza Roxb. The chemical structures of the new compounds were determined to be (7R,10R)-10,11-dihydro-10,11-dihydroxyxanthorrhizol 3-O-b-d- glucopyranoside (1) and (� )-curcuhydroquinone 2,5-di-O-b-d-glucopyranoside (2) on the basis of 1D- and 2D-NMR spectroscopic analyses and optical-rotation characteristics. Compounds 2 and 3 decreased MMP-1 expression in UVB-treated human keratinocytes by ca. 8.9- and 7.6-fold at the mRNA level, and by ca. 9.2- and 6.6-fold at the protein level, respectively. The results indicate that the isolated compounds may have anti-aging effects through inhibition of MMP-1 expression in skin cells.

Department of Physical Medicine & Rehabilitation, Sanggye Paik Hospital, Inje University College of Medicine,Seoul, South KoreaReceived 31 May 2012; accepted 22 May 2013ABSTRACT: Objectives. The aim of this study is toevaluate the accuracy rate of ultrasound (US) -guidedintra-articular (IA) injections in patients by posteriorapproach with osteoarthritis (OA) of the elbow.Methods. Eighty patients with physical examinationand radiographic findings of elbow OA were included.After US-guided IA or palpation-guided IA injection ofiohexol contrast by posterior approach into the elbowjoint, fluoroscopic images were obtained to ascertainwhether the injected material had reached the IA space.Results. Of the 40 injections performed by US guid-ance, 40 were confirmed to have been placed in the IAspace (an accuracy rate of 100%). Thirty-one of the 40injections performed by the palpation guidance wereIA space (77.5% accuracy rate).Conclusions. US-guided IA elbow injections byposterior approach may raise the accuracy rate inelbow joint injections.

Detection of female premutation (PM) carriers of fragile X syndrome may be important in that a PM allele from the mother can expand to a full mutation (FM) when transmitted to the fetus. Although the PM carrier frequency might be different in varying populations, there is a little data on the Korean population. Furthermore, the risks of expansion to FM have not been studied in Korean PM carriers. In this retrospective study, we estimated the female PM carrier frequency and the risks of expansion to FM in Korean diagnostic samples collected for FMR1 gene testing. Of 10,241 pre-conceptional or pregnant women, 13 PM [1 in 788; 95% confidence interval (CI), 1/1 250–1/455] and 75 intermediate allele carriers (1 in 137; 95% CI, 1/172–1/110) were identified. In 26 prenatal diagnoses cases, the PM allele was transmitted to the fetus in 13 pregnancies (50%), and five of these expanded to FM. All of the maternal alleles exceeding 70 repeats expanded to FM. In conclusion, the PM frequency in Korean diagnostic samples was lower than that reported in Western populations, while the risk for FM expansion in alleles exceeding 70 repeats might be higher than expected based upon previous reports.

High-mobility group box 1 (HMGB1) was initially described as a damage-associated-molecular-pattern (DAMP) mediator that worsens acute brain injury after stroke. But, recent findings suggest that HMGB1 can play a surprisingly beneficial role during stroke recovery by promoting endothelial progenitor cell (EPC) function and vascular remodeling in cortical gray matter. Here, we ask whether HMGB1 may also influence EPC responses in white matter injury. The standard lysophosphatidylcholine (LPC) injection model was used to induce focal demyelination in the corpus callosum of mice. Immunostaining showed that within the focal white matter lesions, HMGB1 was up-regulated in GFAP-positive reactive astrocytes, along with the accumulation of Flk1/CD34-double-positive EPCs that expressed pro-recovery mediators such as brain-derived neurotrophic factor and basic fibroblast growth factor. Astrocyte-EPC signaling required the HMGB1 receptor RAGE as treatment with RAGE-neutralizing antibody significantly decreased EPC accumulation. Moreover, suppression of HMGB1 with siRNA in vivo significantly decreased EPC numbers in damaged white matter as well as proliferated endothelial cell numbers. Finally, in vitro cell culture systems confirmed that HMGB1 directly affected EPC function such as migration and tube formation. Taken together, our findings suggest that HMGB1 from reactive astrocytes may attract EPCs to promote recovery after white matter injury.