Postoperative evaluation of modified abductor pollicis longus suspensionplasty using two anchors: Preliminary results.

Among the various surgical treatments for basal joint arthritis, we modified abductor pollicis longus (APL) suspensionplasty by using two anchors. We hypothesized that this modification would prevent not only subsidence but also lateral migration of the first metacarpal. Thirteen thumbs that underwent APL suspensionplasty were investigated. Mean follow-up was 25 months (range, 12-69 months). Clinical and radiographic parameters were assessed preoperatively and postoperatively. Progression of subsidence (trapezial space) and lateral migration of the first metacarpal were investigated sequentially and with the thumb abducted or adducted against stress in a specifically designed mold. Clinical improvement was assessed by decrease in QuickDASH score (from 49.6 to 19.7). The immediate postoperative trapezial space decreased significantly by 39% (p = 0.003), and lateral migration was improved significantly by 14% (p = 0.007). At final follow-up, subsidence and lateral migration had not significantly progressed (p = 0.059 and 0.278, respectively). Under stress, the trapezial space ratio decreased significantly with the thumb in abduction (from 0.63 to 0.59, p = 0.011). APL suspensionplasty using two anchors in patients with basal joint arthritis maintained the position of the first metacarpal bone, and especially lateral subluxation. LEVEL OF EVIDENCE: IV.

Ulnar nerve morphology on magnetic resonance imaging predicts nerve recovery after surgery for cubital tunnel syndrome.

Magnetic resonance imaging (MRI) can evaluate nerve morphology in cubital tunnel syndrome (CuTS), but its value in predicting surgical outcome is unclear. The purpose of this study was to determine whether ulnar nerve morphology on MRI correlated with outcome after CuTS surgery. We reviewed 40 patients who had preoperative MRI and electrodiagnostic (EDX) examinations for CuTS and outcome evaluation 6 months and 2 years postoperatively. Using MRI, ulnar nerve cross-sectional area (UNCSA), changes in signal intensity, and any space-occupying lesion were evaluated. Other factors assessed were age, symptom duration and severity, type-2 diabetes and EDX parameters. Factors associated with unfavorable surgical outcome were identified. At 6 months postoperatively, 12 patients (30%) had excellent, 19 (47.5%) good, 8 (20%) fair and 1 (2.5%) poor results on modified Wilson-Krout criteria. On univariate analysis, unfavorable outcomes were associated with increased UNCSA, space-occupying lesion, and decreased motor nerve conduction velocity (mNCV), and on multivariate analysis with increased UNCSA 1 cm distal from the epicondyle only (model 1) or increased UNCSA 1 cm proximal from the epicondyle and decreased mNCV (model 2). At 2 years, 15 patients (37.5%) had excellent, 21 (52.5%) good, 3 (7.5%) fair and 1 (2.5%) poor results, and no factors correlated with unfavorable outcome. Increased UNCSA on MRI was associated with unfavorable outcome at 6 months but not at 2 years. This study suggests that morphologic ulnar nerve changes can predict delayed nerve recovery after surgery for CuTS.

Improvement in lunate perfusion after radial closing-wedge osteotomy in patients with Kienböck's disease.

Radial closing-wedge osteotomy is a widely accepted treatment for Kienböck's disease. However, despite favorable long-term clinical outcomes, its impact on lunate perfusion has not been documented. The purpose of this study was to determine whether radial closing wedge osteotomy improved lunate perfusion on gadolinium (Gd)-enhanced magnetic resonance imaging (MRI). We conducted a retrospective review of 12 patients with Kienböck's disease who received radial closing wedge osteotomy. Mean age at surgery was 25 years. Preoperative Gd-enhanced MRI was performed in 7 patients. After bone union, implants were removed and MRI was repeated. Two patients were classified as Lichtman stage IIIA, and 5 as stage IIIB. Percentage pre- to post-operative perfused lunate volume was compared on MRI. At last follow-up, mean QuickDASH score improved from 43.7 to 6.2. Pre- to post-operative lunate fragmentation, collapse and perfusion were compared qualitatively on MRI. On quantitative analysis, perfusion increased from 24% to 54% (p = 0.018) using our method of measuring percentage perfused lunate volume. The method showed satisfactory reproducibility. Investigation using Gd-enhanced MRI suggested that radial closing wedge osteotomy increases lunate perfusion.

Antibacterial action of lactoferricin B like peptide against Escherichia coli: reactive oxygen species-induced apoptosis-like death.

AIMS: Emergence and rapid dissemination of antibiotic-resistant bacteria is becoming a severe problem to public health. The search for antimicrobial substitutes for antibiotics is necessary. Lactoferricin B like peptide (LBLP) is a 23-mer antimicrobial peptide (AMP), derived from the big centipede Scolopendra subspinipes mutilans. Although its antifungal effect and its mechanism have been reported, the antibacterial activity has not yet been elucidated. METHOD AND RESULTS: In this study, we investigated antibacterial activity of LBLP and its mode of action. LBLP showed potent antibacterial effect against pathogenic bacteria Escherichia coli and did not show haemolytic activity against human erythrocyte. The general antimicrobial mechanism of AMP is to disrupt the cell membrane, however, LBLP exerted its antibacterial activity by causing apoptosis-like death through reactive oxygen species (ROS) generation. LBLP-treated E. coli cells exhibited hallmarks of apoptosis, such as membrane depolarization, DNA fragmentation, caspase-like protein activation and phosphatidylserine exposure. These apoptotic features were attenuated by pretreatment of NAC, a representative ROS scavenger. CONCLUSIONS: These results demonstrate that LBLP exerted its antibacterial activity by generating ROS and inducing apoptosis-like death in E. coli. LBLP is not membrane destructive per se, but essentially a metabolic inhibitor. SIGNIFICANCE AND IMPACT OF THE STUDY: Lactoferricin B like peptide is potential candidate to replace conventional antibiotics that are less effective because of its unique properties.

Comparison of stratum corneum thickness between two proposed methods of calculation using Raman spectroscopic depth profiling of skin water content.

BACKGROUND/PURPOSE: The stratum corneum (SC) is the most important layer for the barrier function of skin, so investigation of the SC is very important in cosmetic and medical research. Here, we calculated the SC thickness using the depth profile of the skin's water concentration based on previously described methods, and then compared the results. METHODS: Seven Korean women in their 30s participated in this study. Raman spectroscopy was used to measure the in vivo depth profile of skin water concentration. A total of 21 areas were measured at forearm. Microsoft Excel 2007 was used to calculate SC thickness based on the slope and intersection methods. RESULTS: The slope method and the intersection method gave a forearm SC thickness calculated at 21.3 ± 2.6 µm and 17.6 ± 2.8 µm, respectively. There was a significant difference between the two calculation methods but the two methods showed strong correlation of SC thickness results (r = .899). CONCLUSION: Although there was a difference in calculated SC thickness of about 20% between the two methods, these results reveal that the two SC thickness calculation methods using Raman spectroscopy were suitable for measuring SC thickness, a finding consistent with other published results.

Fracture liaison services for osteoporosis in the Asia-Pacific region: current unmet needs and systematic literature review.

The analysis aimed to identify the treatment gaps in current fracture liaison services (FLS) and to provide recommendations for best practice establishment of future FLS across the Asia-Pacific region. The findings emphasize the unmet need for the implementation of new programs and provide recommendations for the refinement of existing ones. The study's objectives were to evaluate fracture liaison service (FLS) programs in the Asia-Pacific region and provide recommendations for establishment of future FLS programs. A systematic literature review (SLR) of Medline, PubMed, EMBASE, and Cochrane Library (2000-2017 inclusive) was performed using the following keywords: osteoporosis, fractures, liaison, and service. Inclusion criteria included the following: patients ≥ 50 years with osteoporosis-related fractures; randomized controlled trials or observational studies with control groups (prospective or retrospective), pre-post, cross-sectional and economic evaluation studies. Success of direct or indirect interventions was assessed based on patients' understanding of risk, bone mineral density assessment, calcium intake, osteoporosis treatment, re-fracture rates, adherence, and mortality, in addition to cost-effectiveness. Overall, 5663 unique citations were identified and the SLR identified 159 publications, reporting 37 studies in Asia-Pacific. These studies revealed the unmet need for public health education, adequate funding, and staff resourcing, along with greater cooperation between departments and physicians. These actions can help to overcome therapeutic inertia with sufficient follow-up to ensure adherence to recommendations and compliance with treatment. The findings also emphasize the importance of primary care physicians continuing to prescribe treatment and ensure service remains convenient. These findings highlight the limited evidence supporting FLS across the Asia-Pacific region, emphasizing the unmet need for new programs and/or refinement of existing ones to improve outcomes. With the continued increase in burden of fractures in Asia-Pacific, establishment of new FLS and assessment of existing services are warranted to determine the impact of FLS for healthcare professionals, patients, family/caregivers, and society.

Recombinant growth hormone therapy for prepubertal children with idiopathic short stature in Korea: a phase III randomized trial.

PURPOSE: Several studies have evaluated the effects of growth hormone (GH) on auxological and biochemical parameters in children with non-GH-deficient, idiopathic short stature (ISS). This study evaluated the efficacy and safety of Growtropin®-II (recombinant human GH) in Korean patients with ISS. METHODS: This was a 1-year, open-label, multicenter, phase III randomized trial of Growtropin®-II in Korean patients with ISS. In total, 70 prepubertal subjects (39 males, 31 females) between 4 and 12 years of age were included in the study. All patients were naive to GH treatment. RESULTS: Annual height velocity was significantly higher in the treatment group (10.68 ± 1.95 cm/year) than the control group (5.72 ± 1.72, p < 0.001). Increases in height and weight standard deviation scores (SDSs) at 26 weeks were 0.63 ± 0.16 and 0.64 ± 0.46, respectively, for the treatment group, and 0.06 ± 0.15 and 0.06 ± 0.28, respectively, for the control group (p < 0.001). Serum insulin-like growth factor (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) increased significantly in the treatment group at week 26 compared to baseline. However, the SDS for body mass index (BMI) at 26 weeks did not change significantly in either group. Growtropin®-II was well tolerated and safe over 1 year of treatment. CONCLUSIONS: One-year GH treatment for prepubertal children with ISS demonstrated increased annualized velocity, height and weight SDSs, and IGF-1 and IGFBP-3 levels, with a favorable safety profile. Further evaluations are needed to determine the optimal dose, final adult height, and long-term effects of ISS treatment.

Tunable quad-band transmission response, based on single-layer metamaterials.

We investigated the electromagnetically induced transparency (EIT)-like effects in planar metamaterials (MMs) at microwave (GHz) frequencies. The specific MMs that were used in this study consist of cut-wire resonator/ring resonator, which achieved the dual EIT-like effects in a single-layer through the bright- and quasi-dark-mode coupling and the lattice mode coupling. In addition, by varying the distance between the two resonators, the quad-band EIT spectral response in the microwave region was obtained, and the group refractive index at the EIT-like resonance of proposed design reached up to 4,000. This study provides the design approach to the multispectral EIT-like effects and might suggest potential applications in a variety of fields, for example, low-loss slow-light device, multiple switching sensor, and other sensing devices.

Comparison of the sensitivity and specificity of p16/Ki-67 dual staining and HPV DNA testing of abnormal cervical cytology in the detection of histology proven cervical intraepithelial neoplasia grade 2 and above (CIN 2+).

INTRODUCTION: Human papillomavirus (HPV) testing is used as a means of triaging cervico-vaginal smears with low grade squamous abnormalities or as part of co-testing with cytology. While HPV testing has a high sensitivity, it has a low specificity in detecting cervical intraepithelial neoplasia grade 2 and above (CIN 2+) leading to unnecessary colposcopy referrals. We investigate the accuracy of the p16/Ki-67 dual immunocytochemical stain in determining the presence of CIN 2+ lesions on histology and its potential as a superior biomarker for triage. METHODS: Liquid based cervico-vaginal cytology specimens with squamous abnormalities and corresponding histology from 97 women with subsequent colposcopy and biopsy were included. The specimens were then subjected to the dual stain and Roche Cobas 4800 multiplex real time PCR HPV DNA testing. The sensitivity and specificity of the dual stain and HPV testing were calculated using CIN 2+ on histology as a reference standard. RESULTS: The sensitivity and specificity of the dual stain in detecting histology proven CIN 2+ was 93.7% and 76.5% while HPV testing was 85.7% and 14.7% respectively. Of the 44 women with ASCUS or LSIL on cytology, the dual stain also reduced the number of unnecessary colposcopy referrals from 27 to 7 when used as a triage marker compared to HPV testing. CONCLUSION: p16/Ki-67 dual stain was more sensitive and specific than HPV testing in determining the presence of CIN 2+ on histology. It could triage low grade cervico-vaginal specimens more effectively and potentially help women avoid unnecessary colposcopies. Future studies are needed to further evaluate its role in cervical cancer screening programmes.

Analysis of pelvic fracture pattern and overall orthopaedic injury burden in children sustaining pelvic fractures based on skeletal maturity.

PURPOSE: The purpose of this study was to review pelvic fractures and concomitant orthopaedic injuries in children who have a patent triradiate cartilage (TRO) compared with children whose triradiate cartilage has closed (TRC). We hypothesise that these injuries will differ, leading to correlated alterations in management. PATIENTS AND METHODS: Using a database, we retrospectively reviewed patients aged below 18 years with pelvic fractures presenting to our Level 1 trauma center. Radiographs and CT scans were reviewed to identify orthopaedic injuries and categorise pelvic injuries using the modified Torode classification between the two groups. RESULTS: A total of 178 patients met inclusion criteria (60 TRO and 118 TRC). Mean age ± SD for TRO and TRC groups were 8 ± 4 years and 16 ± 2 years, respectively. TRO patients were more likely to present as a pedestrian struck by a vehicle (odds ratio (OR) 6.0; p < 0.001) and less likely to present after a motor vehicle collision (OR 0.2; p < 0.001). TRO patients were more likely to sustain rami fractures (OR 2.1; p = 0.020) and Torode IIIA injuries (OR 3.6; p < 0.001). They were less likely to sustain acetabular fractures (OR 0.5; p = 0.042), sacral fractures (OR 0.4; p = 0.009), hip dislocations (p = 0.002) and Torode IV injuries (OR 0.4; p = 0.004). TRO patients were less likely to be treated operatively for their pelvic (OR 0.3; p = 0.013) and orthopaedic injuries (OR 0.4; p = 0.006). CONCLUSION: We suggest that patients with open triradiate cartilage are unique. Their pelvic injuries may be treated more conservatively as they have a greater potential for periosteal healing and bone remodelling. Patients with closed triradiate cartilage should be treated similarly to adults, as they share a similar mechanism of injury and need for operative fixation.

Switching and extension of transmission response, based on bending metamaterials.

The electromagnetically-induced transparency (EIT)-like effects in planar and non-planar metamaterials (MMs) were investigated for microwave (GHz) frequencies. The specific MMs used in this study consisted of a cut-wire resonator and a ring resonator, where were placed on the top and the bottom layers, respectively. A transmission window was produced, due to the interference between bright- and bright-mode coupling. Using the numerical and the experimental results, we demonstrate that the bending of MM leads to enhanced transmission and bandwidth, as well as an additional EIT-like peak. This provides an effective way of realizing the tunable devices, including the switching sensors.

Multifractal anisotropic swimming: the optimal foraging behaviour of grouper larvae.

It was hypothesized that the Malabar grouper Ephinephelus malabaricus larvae have developed search patterns adapted to the distribution of their prey to maximise their net energy intake per unit time. Analysis of the swimming behaviour of E. malabaricus larvae in both the presence and absence of Artemia sp. nauplii is presented to test this hypothesis. A method derived from turbulence studies (the moment function of the displacements) was used to characterize the behaviour. The results revealed that larval swimming pattern was multifractal (intermittent and long-range-correlated) and isotropic (i.e. uniform in all directions) in the presence of prey, but multifractal and anisotropic (i.e. more frequent long displacement on the vertical axis) in the absence of prey. It is suggested that the search behaviour observed in the absence of prey is an adaptive response to prey distribution pattern, which is often characterised by multifractality and anisotropy (i.e. larger patches on the horizontal axes). In the presence of prey, E. malabaricus shifted to intensive search behaviour. Other possible contributors to the observed patterns are discussed. It is concluded that multifractality and anisotropy of swimming patterns observed in the experiment are mainly explained in an optimal foraging theory framework.

Peroxisome proliferator-activated receptor δ inhibits Porphyromonas gingivalis lipopolysaccharide-induced activation of matrix metalloproteinase-2 by downregulating NADPH oxidase 4 in human gingival fibroblasts.

We investigated the roles of peroxisome proliferator-activated receptor δ (PPARδ) in Porphyromonas gingivalis-derived lipopolysaccharide (Pg-LPS)-induced activation of matrix metalloproteinase 2 (MMP-2). In human gingival fibroblasts (HGFs), activation of PPARδ by GW501516, a specific ligand of PPARδ, inhibited Pg-LPS-induced activation of MMP-2 and generation of reactive oxygen species (ROS), which was associated with reduced expression of NADPH oxidase 4 (Nox4). These effects were significantly smaller in the presence of small interfering RNA targeting PPARδ or the specific PPARδ inhibitor GSK0660, indicating that PPARδ is involved in these events. In addition, modulation of Nox4 expression by small interfering RNA influenced the effect of PPARδ on MMP-2 activity, suggesting a mechanism in which Nox4-derived ROS modulates MMP-2 activity. Furthermore, c-Jun N-terminal kinase and p38, but not extracellular signal-regulated kinase, mediated PPARδ-dependent inhibition of MMP-2 activity in HGFs treated with Pg-LPS. Concomitantly, PPARδ-mediated inhibition of MMP-2 activity was associated with the restoration of types I and III collagen to levels approaching those in HGFs not treated with Pg-LPS. These results indicate that PPARδ-mediated downregulation of Nox4 modulates cellular redox status, which in turn plays a critical role in extracellular matrix homeostasis through ROS-dependent regulation of MMP-2 activity.

Low Frequency of MKRN3 Mutations in Central Precocious Puberty Among Korean Girls.

Mutations of MKRN3, the gene encoding makorin RING-finger protein 3, lead to central precocious puberty (CPP). The aim of this study was to investigate mutations of the MKRN3 gene in Korean girls with CPP. Two hundred-sixty Korean girls with idiopathic CPP were included. Auxological and endocrine parameters were measured, and the entire MKRN3 gene was directly sequenced. MKRN3 gene analysis revealed one novel nonsense mutation (p.Gln281 *) and 6 missense variants (p.Ile100Phe, p.Gly196Val, p.Ile204Thr, p.Gln226Pro, p.Lys233Asn, and p.Ser396Arg). The novel nonsense mutation (p.Gln281 *) was a heterozygous C>T nucleotide change (c.841C>T) predicted to result in a truncated protein due to a premature stop codon in the MKRN3 gene. The nonsense mutation (p.Gln281 *) was only identified in one of the girls and her younger brother. Compared to previous reports on MKRN3 mutations in familial and sporadic cases of CPP, the present study reveals a relatively low number of MKRN 3 mutations in Korean girls with CPP. Larger samples of children with CPP and MKRN3 mutations are necessary in order to clarify whether the clinical course of puberty may differ as compared to idiopathic CPP.

The Association between Bone Age Advancement and Insulin Resistance in Prepubertal Obese Children.

OBJECTIVE: Obesity is associated with bone age (BA) advancement, but the underlying mechanisms remain unclear. The objective of this study was to investigate the association between BA maturation and insulin levels in obese children. METHODS: In this cross-sectional study of 93 prepubertal obese children, anthropometric data and hormonal values were measured. Subjects were divided into 2 groups based on the difference between BA and chronological age (CA) (noted as BA-CA). RESULTS: The study population included 39 (41.9%) males and 54 (58.1%) females with a mean age of 7.4±1.5 years. The advanced bone age group defined as BA-CA>1 year (n=44) had significantly higher HOMA-IR and fasting insulin levels, and lower quantitative insulin sensitivity check index (QUICKI). BA-CA was significantly correlated with fasting insulin (r=0.255, P=0.014), HOMA-IR (r=0.230, P=0.027), and QUICKI (r=- 0.301, P=0.003). Also, height SDS was significantly associated with ΔBA-CA (r=0.417, P<0.001). In the multiple regression analysis, HOMA-IR was identified as a significant independent predictor of BA-CA. CONCLUSION: Bone age is more advanced in obese children with hyperinsulinemia and insulin resistance. These findings suggest that insulin may affect skeletal maturation.

Validation of the traditional Chinese version of the Menopausal Rating Scale with WHOQOL-BREF.

Objective To assess the criterion validity, construct validity and test-retest reliability of the traditional Chinese language version of the Menopause Rating Scale (MRS-TC version). Methods This was an observational, cross-sectional study covering hospital and community samples of 317 women aged 39-62 years. Two questionnaires were administered, namely, the MRS-TC version, made up of 11 items in three dimensions, and the World Health Organization Quality of Life-BREF (WHOQOL-BREF). The intraclass correlation coefficient was used to examine the test-retest reliability of the questionnaire on two separate occasions, 2 weeks apart. The internal consistency was assessed with Cronbach's α. To evaluate criterion validity, the relationship between the individual items and dimension scores of both instruments was estimated. Pearson's correlation was used to assess convergent and discriminant validity; construct validity was evaluated by comparing the mean scores of menopausal and non-menopausal women for each of the MRS dimensions. Results The final questionnaire comprised 11 items in three dimensions. The intra-class correlation (ICC) for the test-retest reliability ranged from 0.83 to 0.93; values of Cronbach's α for psychological, somatic, and urogenital symptom domains were 0.88, 0.68, and 0.59, respectively. For the convergent and discriminant validity, the correlations between the individual questionnaire and the WHOQOL-BREF were significant; those with the MRS dimensions were significantly negatively associated for the physical, psychological, social and environmental domains. Conclusion The MRS-TC version using the traditional Chinese language is a reliable and valid questionnaire for assessing menopausal symptoms and global quality of life in climacteric women.

Early menarche increases the risk of Type 2 diabetes in young and middle-aged Korean women.

AIMS: To investigate the association between early menarche (menarche age < 12 years) and Type 2 diabetes mellitus in young and middle-aged Korean women. METHODS: We analysed data for 4657 women aged 20-50 years from the Fourth Korea National Health and Nutrition Examination Survey (KNHANES IV) (2007-2009). RESULTS: The prevalence of Type 2 diabetes was 2.8%. Women with early menarche had a higher prevalence of impaired fasting glucose than did women with later menarche (age ≥ 12 years) in the 20-30 age group (7.4% vs. 3.0%), and a higher prevalence of diabetes in the 30-40 (6.3% vs. 1.7%) and 40-50 (18.5% vs. 4.4%) age groups. The odds ratio (OR) of Type 2 diabetes in women with early menarche was 3.61 [95% confidence interval (CI), 1.90-6.88] after adjusting for age. In multivariate regression, the OR of Type 2 diabetes decreased to 2.52 (95% CI, 1.29-4.94) after further adjusting for BMI. However, the OR decreased to 2.04 (95% CI, 0.95-4.39) without significance after adjusting for HOMA-IR. CONCLUSIONS: Early menarche increased the risk of Type 2 diabetes in young and middle-aged Korean women although adulthood adiposity attenuated the relationship. Knowledge of age at menarche is important in identifying women at risk for diabetes.

Changing social contact patterns under tropical weather conditions relevant for the spread of infectious diseases.

Weather conditions and social contact patterns provide some clues to understanding year-round influenza epidemics in the tropics. Recent studies suggest that contact patterns may direct influenza transmission in the tropics as critically as the aerosol channel in temperate regions. To examine this argument, we analysed a representative nationwide survey dataset of contact diaries with comprehensive weather data in Taiwan. Methods we used included model-free estimated relative changes in reproduction number, R 0; relative changes in the number of contacts; and model-based estimated relative changes in mean contacts using zero-inflated negative binomial regression models. Overall, social contact patterns clearly differ by demographics (such as age groups), personal idiosyncrasies (such as personality and happiness), and social institutions (such as the division of weekdays and weekend days). Further, weather conditions also turn out to be closely linked to contact patterns under various circumstances. Fleeting contacts, for example, tend to diminish when it rains hard on weekdays, while physical contacts also decrease during weekend days with heavy rain. Frequent social contacts on weekdays and under good weather conditions, including high temperature and low absolute humidity, all might facilitate the transmission of infectious diseases in tropical regions.

Ligand-activated peroxisome proliferator-activated receptor-δ and -γ inhibit lipopolysaccharide-primed release of high mobility group box 1 through upregulation of SIRT1.

Peroxisome proliferator-activated receptors (PPARs) inhibit lipopolysaccharide (LPS)-primed release of high mobility group box 1 (HMGB1), a late proinflammatory mediator, but the underlying molecular mechanism is not completely understood. In this study, we demonstrated that the inhibition of HMGB1 release by PPAR-δ and -γ is associated with the deacetylase activity of SIRT1. Ligand-activated PPAR-δ and -γ inhibited LPS-primed release of HMGB1, concomitant with elevation in SIRT1 expression and promoter activity. These effects were significantly reduced in the presence of small interfering (si)RNAs against PPAR, indicating that PPAR-δ and -γ are involved in both HMGB1 release and SIRT1 expression. In addition, modulation of SIRT1 expression and activity by siRNA or chemicals correspondingly influenced the effects of PPARs on HMGB1 release, suggesting a mechanism in which SIRT1 modulates HMGB1 release. Furthermore, we showed for the first time that HMGB1 acetylated in response to LPS or p300/CBP-associated factor (PCAF) is an effective substrate for SIRT1, and that deacetylation of HMGB1 is responsible for blockade of HMGB1 release in macrophages. Finally, acetylation of HMGB1 was elevated in mouse embryonic fibroblasts from SIRT1-knockout mice, whereas this increase was completely reversed by ectopic expression of SIRT1. These results indicate that PPAR-mediated upregulation of SIRT1 modulates the status of HMGB1 acetylation, which, in turn, has a critical role in the cellular response to inflammation through deacetylation-mediated regulation of HMGB1 release.

Identification of a novel antimicrobial peptide, scolopendin 1, derived from centipede Scolopendra subspinipes mutilans and its antifungal mechanism.

In this study, a novel antimicrobial peptide, scolopendin 1, was identified from adult centipedes, Scolopendra subspinipes mutilans using RNA sequencing. Scolopendin 1 exerted an antimicrobial activity without inducing haemolysis of human erythrocytes. In order to understand the antifungal mechanism, a reactive oxygen species (ROS) assay was performed, which indicated that scolopendin 1 induced ROS accumulation in Candida albicans. Evaluation of fungal viability using N-acetyl cysteine, a ROS scavenger, suggested that ROS are a major factor in scolopendin 1-induced fungal cell death. Co-staining of annexin V-fluorescein isothiocyanate (FITC) and propidium iodide, and TUNEL and 4',6-diamidino-2-phenylindole (DAPI) assays confirmed that ROS-induced fungal cell death is associated with apoptosis. To further investigate the mechanism that facilitates the progression of apoptosis, changes in intracellular Ca(2+) concentration and mitochondrial dysfunction were examined. Ca(2+) , a signalling molecule in the apoptotic pathway, was increased in the cytosol and mitochondria, and ROS accumulation triggered mitochondrial depolarization and the release of cytochrome c, a pro-apoptotic factor, from the mitochondria to the cytosol. Finally, the released cytochrome c activated intracellular caspase. The present study suggests that scolopendin 1 could emerge as a model molecule that targets the apoptotic pathway and provides a novel remedy.