Increasing brown adipocytes activity and inducting browning of white adipocytes are potential therapeutic targets for the treatment of obesity. In the present study, we investigated the effects of ...Tanshinone 1 (Tan 1), a major compound from Salvia miltiorrhiza Bunge, on the activation of brown adipocytes and browning of white adipocytes in vivo and in vitro.
Expression of genes associated with brown adipocyte function including thermogenesis, mitochondria biogenesis and fatty acid oxidation was examined in brown adipose tissue (BAT) and white adipose tissue (WAT) of high fat diet (HFD)-fed obese mice administrated with Tan 1 or in immortalized brown adipocytes (iBAs) and 3T3-L1 adipocytes treated with Tan 1. Mitochondria DNA (mtDNA) content, lipolysis and phosphorylated AMP-activated protein kinase (AMPK) were further assessed in Tan 1 treated-iBAs and 3T3-L1 adipocytes.
The administration of Tan 1 protected against HFD-induced obesity in mice, which was associated with enhanced expression of brown adipocyte function-related genes in BAT and WAT. Tan 1 treatment also upregulated brown adipocyte function-related genes in iBA and induced beige adipocytes genes in 3T3-L1 adipocytes, resulting in increased mtDNA content and lipolysis. Tan 1 activated AMPK in BAT and WAT of HFD-fed obese mice as well as in iBAs and 3T3-L1 adipocytes. Inhibition of AMPK by compound C prevented Tan 1-induced expression of beige adipocytes genes.
These results indicate that Tan 1 activates brown adipocytes and induces browning of white adipocytes, which may contribute to anti-obesity activity of Tan 1.
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Although the measurement of coronal alignment of the lower limb on conventional full-length weight-bearing anteroposterior (FLWAP) radiographs was reported to be influenced by the knee joint ...rotation, no comparative analysis was performed considering the effects of knee joint rotation on the sagittal and axial planes simultaneously using the three-dimensional images while taking into account the actual weight-bearing conditions. The aim of this study was to investigate the effect of knee joint rotation on the measurement accuracy of coronal alignment of the lower limb on the FLWAP radiograph.
Radiographic images of 90 consecutive patients (180 lower limbs) who took both the FLWAP radiograph and the EOS image were retrospectively reviewed. The relationship among delta values of mechanical tibiofemoral angle (mTFA) between the FLWAP radiographs and the EOS images (ΔmTFA), knee flexion/extension angle (sagittal plane rotation) on the EOS images, and patellar rotation (axial plane rotation) on the FLWAP radiographs were analyzed. Further, subgroup analysis according to each direction of knee joint rotation was performed.
There was a significant correlation between ΔmTFA and sagittal plane rotation (r = 0.368, P < 0.001), whereas axial plane rotation was not correlated. In the analysis according to the direction, statistically significant correlation was observed only in the knee flexion group (r = 0.399, P < 0.001). The regression analysis showed a significant linear relationship between ΔmTFA and sagittal plane rotation (r
= 0.136, P < 0.001). Additional subgroup analysis in patients with the patellar rotation greater than 3% showed a similar result of a linear relationship between ΔmTFA and sagittal plane rotation (r
= 0.257, P < 0.001), whereas no statistically significant relationship was found in patients with the patellar rotation less than 3%.
The measurement accuracy of coronal alignment of the lower limb on the FLWAP radiographs would be influenced by knee flexion, specifically when there is any subtle rotation of the knee joint in the axial plane. A strict patellar forward position without axial plane rotation of the knee could provide accurate results of the measurement even if there is a fixed flexion contracture of the knee.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
ABSTRACT
Altered energy balance and insulin resistance are important characteristics of aging. Skeletal muscle is a major site of glucose disposal, and the role of aging‐associated inflammation in ...skeletal muscle insulin resistance remains unclear. To investigate, we examined glucose metabolism in 18‐mo‐old transgenic mice with muscle‐specific overexpression of IL‐10 (MIL10) and in wild‐type mice during hyperinsulinemic‐euglycemic clamping. Despite similar fat mass and energy balance, MIL10 mice were protected from aging‐associated insulin resistance with significant increases in glucose infusion rates, whole‐body glucose turnover, and skeletal muscle glucose uptake (~60%; P <0.05), as compared to age‐matched WT mice. This protective effect was associated with decreased muscle inflammation, but no changes in adipose tissue inflammation in aging MIL10 mice. These results demonstrate the importance of skeletal muscle inflammation in aging‐mediated insulin resistance, and our findings further implicate a potential therapeutic role of anti‐inflammatory cytokine in the treatment of aging‐mediated insulin resistance.—Dagdeviren, S., Jung, D. Y., Friedline, R. H., Noh, H. L., Kim, J. H., Patel, P. R., Tsitsilianos, N., Inashima, K., Tran, D. A., Hu, X., Loubato, M. M., Craige, S. M., Kwon, J. Y., Lee, K. W., Kim, J. K. IL‐10 prevents aging‐associated inflammation and insulin resistance in skeletal muscle. FASEB J. 31, 701–710 (2017). http://www.fasebj.org
We conducted a phase 3 randomized trial comparing 2 different doses of daunorubicin as induction chemotherapy in young adults (60 years of age or younger) with acute myeloid leukemia (AML). Of 383 ...patients who were analyzed, 189 received standard-dose daunorubicin (SD-DN, 45 mg/m2 per day times 3 days) and 194 received high-dose daunorubicin (HD-DN, 90 mg/m2 per day times 3 days) in addition to cytarabine (200 mg/m2 per day times 7 days) to induce complete remission (CR). The CR rates were 72.0% in the SD-DN arm and 82.5% in the HD-DN arm (P = .014). At a median follow-up of 52.6 months, overall (OS) and event-free (EFS) survival were higher in the HD-DN arm than in the SD-DN arm (OS, 46.8% vs 34.6%, P = .030; EFS, 40.8% vs 28.4%, P = .030). Differences in CR rate and both OS and EFS remained significant after adjusting for other variables (CR, hazard ratio HR, 1.802, P = .024; OS, HR, 0.739, P = .032; EFS, HR, 0.774, P = .048). The survival benefits of HD-DN therapy were evident principally in patients with intermediate-risk cytogenetic features. The toxicity profiles were similar in the 2 arms. In conclusion, HD-DN improved both the CR rate and survival duration compared with SD-DN in young adults with AML. This study is registered at www.clinicaltrials.gov as #NCT00474006.
Radotinib is a second-generation BCR-ABL1 tyrosine kinase inhibitor (TKI) approved in Korea for chronic phase chronic myeloid leukemia (CML-CP) in patients newly diagnosed or with insufficient ...response to other TKIs. This study was conducted to evaluate the efficacy and safety of radotinib as first-line therapy for CML-CP.
This multinational, open-label study assigned patients (1:1:1) to one of two twice-daily radotinib doses, or imatinib daily. The primary endpoint was major molecular response (MMR) by 12 months.
Two hundred forty-one patients were randomized to receive radotinib 300 mg (
= 79) or 400 mg twice-daily (
= 81), or imatinib 400 mg daily (
= 81). MMR rates by 12 months were higher in patients receiving radotinib 300 mg (52%) or radotinib 400 mg twice-daily (46%) versus imatinib (30%;
= 0.0044 and
= 0.0342, respectively). Complete cytogenetic response (CCyR) rates by 12 months were higher for radotinib 300 mg (91%) versus imatinib (77%;
= 0.0120). Early molecular response at 3 months occurred in 86% and 87% of patients receiving radotinib 300 mg and radotinib 400 mg, respectively, and 71% of those receiving imatinib. By 12 months, no patients had progression to accelerated phase or blast crisis. Most adverse events were manageable with dose reduction.
Radotinib demonstrated superiority over imatinib in CCyR and MMR in patients newly diagnosed with Philadelphia chromosome-positive CML-CP. This trial was registered at www.clinicaltrials.gov as NCT01511289
.
As the most successful platform for peer-based accommodation sharing, Airbnb has transformed the lodging industry into something much more affordable and accessible for travelers on a budget. ...Compared to a hotel stay, however, its variability of facility and service has created guests' negative emotions such as regret and dissatisfaction. These emotions may cause stress, which negatively affect mental health. Therefore, we explore the factors that influence Airbnb guests' regret, and investigate the relationship between their regret, dissatisfaction, and negative behavioral intention. Structural equation model is utilized on a total of 456 U.S. consumers to examine the relationship among Airbnb users' responses. The findings indicate that price perception influences regret and dissatisfaction the most. The study also reveals that regret has a positive correlation with dissatisfaction, while does not have an influence on switching intention and negative word of mouth. Based on the result, theoretical and managerial implications are discussed.
Though Forkhead box P (FOXP) transcription factors comprising of FOXP1, FOXP2, FOXP3 and FOXP4 are involved in the embryonic development, immune disorders and cancer progression, the underlying ...function of FOXP3 targeting CD4 + CD25+ regulatory T (Treg) cells and the dual roles of FOXP proteins as an oncogene or a tumor suppressor are unclear and controversial in cancers to date. Thus, the present review highlighted research history, dual roles of FOXP proteins as a tumor suppressor or an oncogene, their molecular networks with other proteins and noncoding RNAs, cellular immunotherapy targeting FOXP3, and clinical implications in cancer progression.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Purpose We compared two induction regimens, idarubicin (12 mg/m
/d for 3 days) versus high-dose daunorubicin (90 mg/m
/d for 3 days), in young adults with newly diagnosed acute myeloid leukemia ...(AML). Patients and Methods A total of 299 patients (149 randomly assigned to cytarabine plus idarubicin AI and 150 assigned to cytarabine plus high-dose daunorubicin AD) were analyzed. All patients received cytarabine (200 mg/m
/d for 7 days). Results Complete remission (CR) was induced in 232 patients (77.6%), with no difference in CR rates between the AI and AD arms (80.5% v 74.7%, respectively; P = .224). At a median follow-up time of 34.9 months, survival and relapse rates did not differ between the AI and AD arms (4-year overall survival, 51.1% v 54.7%, respectively; P = .756; cumulative incidence of relapse, 35.2% v 25.1%, respectively; P = .194; event-free survival, 45.5% v 50.8%, respectively; P = .772). Toxicity profiles were also similar in the two arms. Interestingly, overall and event-free survival times of patients with FLT3 internal tandem duplication (ITD) mutation were significantly different (AI v AD: median overall survival, 15.5 months v not reached, respectively; P = .030; event-free survival, 11.9 months v not reached, respectively; P = .028). Conclusion This phase III trial comparing idarubicin with high-dose daunorubicin did not find significant differences in CR rates, relapse, and survival. Significant interaction between the treatment arm and the FLT3-ITD mutation was found, and high-dose daunorubicin was more effective than idarubicin in patients with FLT3-ITD mutation.
Epoxy resin is used for the powder coatings of steel pipes, but paints containing epoxy resins may cause various structural changes, including methyl abstraction, depending on climatic conditions and ...ultraviolet ray intensity. Structural changes cause the deterioration of various properties. Herein, the degradation mechanism of weathering resistance was analyzed by monitoring molecular structure changes of bisphenol A diglycidyl ether (BADGE)-dicyandiamide (DDA)-cured coating films before and after the Weather-O-Meter test (accelerated weather resistance chamber). DSC(Differential scanning calorimetry), GPC (Gel permeation chromatography), FT-IR(Fourier-transform Infrared spectroscopy), FT-NMR(Fourier-transform nuclear magnetic resonance), and MALDI-TOF MS(Matrix-assisted laser desorption ionization time-of-flight mass spectroscopy) analyses were performed on coated specimens. Structural changes, including epoxy resin oxidation and cross-linking bond breakage, were confirmed while the chain cleavage and crosslinking occurred simultaneously.
•The results of this paper provide degradation mechanism information of FBE (Fusion-bonded epoxy) through analysis data about cured structure changed.
Background:
Conflicting results have been reported concerning the progression of medial meniscal extrusion (MME) after arthroscopic transtibial pull-out repair of medial meniscus posterior root tear ...(MMRT), and no study has evaluated the relevant factors affecting the progression of MME.
Purpose:
To (1) evaluate the subjective and objective surgical outcomes of arthroscopic transtibial pull-out repair of MMRT and (2) identify relevant factors affecting the progression of MME after surgery.
Study Design:
Case-control study; Level of evidence, 3.
Methods:
A total of 63 patients who underwent isolated arthroscopic transtibial pull-out repair of MMRT between January 2010 and June 2017 were evaluated retrospectively. Clinical scores and various radiographic parameters were evaluated to assess the surgical outcomes. The patients were classified into 2 groups according to the change in medial meniscal extrusion ratio (MMER) at 1 year after surgery compared with before surgery (group 1 consisted of 21 patients with reduced or maintained MMER; group 2 consisted of 42 patients with increased MMER). Variables including baseline demographics, radiographic parameters, and arthroscopic findings were compared to identify relevant factors affecting the progression of MME after surgery.
Results:
In the overall cohort, clinical outcomes at postoperative 2 years improved significantly (P < .001 for visual analog scale score, International Knee Documentation Committee subjective score, and Lysholm score), whereas radiographic parameters showed an overall deterioration compared with the preoperative level. In subgroup comparisons, a significant difference was seen in the time from the onset of symptoms until surgery (P < .001), defined as preoperative symptom duration, which a subsequent logistic regression analysis revealed to be a relevant factor associated with the progression of MMER (P = .015). Both groups showed progression of radiographic osteoarthritis, but the progression was significantly higher in group 2 compared with group 1 at postoperative 2 years (P = .032). On receiver operating characteristic curve analysis, the cutoff point for preoperative symptom duration associated with the progression of MMER was 13 weeks (sensitivity, 52.4%; specificity, 76.2%; accuracy, 72.4%).
Conclusion:
The arthroscopic transtibial pull-out repair of MMRT showed clinical improvement but did not prevent the progression of knee osteoarthritis, MME, or MMER. Although the preservation of MMER was not capable of completely preventing the progression of knee degeneration, MMER still has a potential clinical value in delaying the rate of progression of knee degeneration. Early surgical repair of MMRT, within 13 weeks from the onset of symptoms, might be helpful to prevent the progression of MME.
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