Aims/hypothesis
Obesity and insulin resistance are associated with low-grade chronic inflammation. Glucagon-like peptide-1 (GLP-1) is known to reduce insulin resistance. We investigated whether GLP-1 ...has anti-inflammatory effects on adipose tissue, including adipocytes and adipose tissue macrophages (ATM).
Methods
We administered a recombinant adenovirus (rAd) producing GLP-1 (rAd-GLP-1) to an
ob/ob
mouse model of diabetes. We examined insulin sensitivity, body fat mass, the infiltration of ATM and metabolic profiles. We analysed the mRNA expression of inflammatory cytokines, lipogenic genes, and M1 and M2 macrophage-specific genes in adipose tissue by real-time quantitative PCR. We also examined the activation of nuclear factor κB (NF-κB), extracellular signal-regulated kinase 1/2 and Jun N-terminal kinase (JNK) in vivo and in vitro.
Results
Fat mass, adipocyte size and mRNA expression of lipogenic genes were significantly reduced in adipose tissue of rAd-GLP-1-treated
ob/ob
mice. Macrophage populations (F4/80
+
and F4/80
+
CD11b
+
CD11c
+
cells), as well as the expression and production of IL-6, TNF-α and monocyte chemoattractant protein-1, were significantly reduced in adipose tissue of rAd-GLP-1-treated
ob/ob
mice. Expression of M1-specific mRNAs was significantly reduced, but that of M2-specific mRNAs was unchanged in rAd-GLP-1-treated
ob/ob
mice. NF-κB and JNK activation was significantly reduced in adipose tissue of rAd-GLP-1-treated
ob/ob
mice. Lipopolysaccharide-induced inflammation was reduced by the GLP-1 receptor agonist, exendin-4, in 3T3-L1 adipocytes and ATM.
Conclusions/interpretation
We suggest that GLP-1 reduces macrophage infiltration and directly inhibits inflammatory pathways in adipocytes and ATM, possibly contributing to the improvement of insulin sensitivity.
AMoRE is an international project to search for the neutrinoless double beta decay of
100
Mo
using a detection technology consisting of magnetic microcalorimeters (MMCs) and molybdenum-based ...scintillating crystals. Data collection has begun for the current AMORE-I phase of the project, an upgrade from the previous pilot phase. AMoRE-I employs thirteen
48
depl
.
Ca
100
MoO
4
crystals and five
Li
2
100
MoO
4
crystals for a total crystal mass of 6.2 kg. Each detector module contains a scintillating crystal with two MMC channels for heat and light detection. We report the present status of the experiment and the performance of the detector modules.
Although the hyper-glycosylated transmembrane protein Mucin 1 (MUC1) is aberrantly overexpressed in human breast carcinoma, the biological significance of MUC1 overexpression is unclear. This study ...showed that MUC1 expression promoted the synthesis and secretion of vascular endothelial growth factor (VEGF) through the AKT signaling pathway. Increase VEGF production through MUC1 expression had a number of effect. First, MUC1 transfection increased expression of VEGF in breast cancer cells. Second, MUC1-mediated VEGF induction was attenuated by a chemical inhibitor of AKT or MUC1 knock-down by MUC1 siRNA. Third, MUC1 expression led to the activation of insulin-like growth factor-1 receptor, which correlated with VEGF expression. In addition, when MDA-MB-231 human breast cancer cells were directly injected into NOD/SCID mice, MUC1 expression accelerated xenograft tumor growth in vivo. Finally, MUC1 expression enhanced tumor growth and angiogenesis in a PyMT-MMTV/hMUC1 transgenic mouse model. Concurrent with these results, analysis of a human tissue microarray identified a high correlation between MUC1 and VEGF expression in human breast carcinoma. The current report is the first to demonstrate that MUC1 expression promotes angiogenesis in human breast cancer in vivo and in vitro.
Summary
Background
Data on the incidence of venous thromboembolism (VTE) following major surgery in Asian populations are limited.
Methods
Using the Korean Health Insurance Review and Assessment ...Service database, we performed a nationwide population‐based epidemiologic study to estimate the incidence of VTE after major orthopedic, cancer, and benign surgeries. VTE cases were identified from all patients undergoing major surgery between 2007 and 2011 using both diagnostic and drug codes as treatment evidence of VTE within 5 weeks of surgery. We also calculated the relative risk of VTE in major orthopedic and cancer surgery compared to benign surgery.
Results
The overall rates of postoperative VTE were 1.24%, 0.67%, and 0.05% for major orthopedic, cancer, and benign surgeries, respectively. Hip fracture (1.60%) and colorectal cancer surgeries (1.67%) were associated with the highest rates of VTE, and the rates steadily increased during the study period. Advanced age, female sex, and general anesthesia were independent risk factors for VTE. Patients undergoing surgery for colorectal, pancreatic, ovarian, and esophageal cancer, and major orthopedic surgery had a > 20‐fold higher risk of VTE than those undergoing benign surgery.
Conclusions
This is the largest epidemiologic study to investigate the incidence of VTE after major surgery in Asia, demonstrating that the rates of postoperative VTE are lower than in Caucasian populations. This study contributes to a better understanding of the differences in postoperative VTE development between Korean and Caucasian populations; the data also suggest that perioperative prophylactic strategies in Asians should be based on studies of such populations.
The Korea Invisible Mass Search (KIMS) collaboration has developed low-background NaI(Tl) crystals that are suitable for the direct detection of WIMP dark matter. Building on experience accumulated ...during the KIMS-CsI programs, the KIMS-NaI experiment will consist of a 200 kg NaI(Tl) crystal array surrounded by layers of shielding structures and will be operated at the Yangyang underground laboratory. The goal is to provide an unambiguous test of the DAMA/LIBRA annual modulation signature. Measurements of six prototype crystals show progress in the reduction of internal contamination from radioisotopes. Based on our understanding of these measurements, we expect to achieve a background level in the final detector configuration that is less than 1 count/day/keV/kg for recoil energies around 2 keV. The annual modulation sensitivity for the KIMS-NaI experiment shows that an unambiguous 7
σ
test of the DAMA/LIBRA signature would be possible with a 600 kg year exposure with this system.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Aims
This study investigated the antiobesity effect of lactic acid bacteria (Lactobacillus plantarum LG42) isolated from gajami sik‐hae.
Methods and Results
Male C57BL/6J mice were divided into four ...groups (n = 10); NDC (normal diet & DW), HDC (high‐fat diet & DW), LGLAB (high‐fat diet & Lactobacillus plantarum LG42, 1 × 107 CFU per mouse), HGLAB (high‐fat diet & L. plantarum LG42, 1 × 109 CFU per mouse). After 12 weeks, GLAB supplemented groups showed lower body weight, with a significant reduction in epididymal and back fat. Serum and hepatic triglyceride, serum insulin and leptin levels were significantly lowered in GLAB supplemented groups. The hepatic mRNA expression of PPARα and CPT‐I were significantly increased in GLAB groups, whereas the level of ACC, SREBP‐1 and LXRα were significantly decreased in GLAB groups compared with HDC group. Additionally, GLAB reduces the expression of PPARγ in the epididymal adipose tissue resulting in inhibition of genes regulated by PPARγ.
Conclusion
These results suggest that the Lactobacillus plantarum LG42 has antiobesity effects in high‐fat‐diet‐induced obese mice.
Significance and Impact of the Study
These results may contribute to nutraceutical and food industries in developing functional food and probiotics based therapies for the treatment and prevention of obesity.
Background: The aim of this study was to determine whether expressions of the excision repair cross-complementing (ERCC1), thymidylate synthase (TS), and glutathione S-transferase P1 (GSTP1) predict ...clinical outcome in patients with advanced gastric cancer treated with fluorouracil (5-fluorouracil)/oxaliplatin chemotherapy. Patients and methods: The study population consisted of 64 advanced gastric cancer patients (median age 51 years). Patients were treated with oxaliplatin 85 mg/m2 as a 2-h infusion at day 1 plus leucovorin 20 mg/m2 over 10 min, followed by 5-FU bolus 400 mg/m2 and 22-h continuous infusion of 600 mg/m2 at days 1–2. Treatment was repeated in 2-week intervals. The expressions of ERCC1, TS, and GSTP1 of primary tumors were examined by immunohistochemistry. Results: The positive rates of ERCC1, TS, and GSTP1 were 70.3%, 29.7%, and 50.0%, respectively. The patients without ERCC1 expression were more likely to respond to chemotherapy (P = 0.045). There were no significant differences between response and TS or GSTP1 expression pattern (P = 0.813, P = 0.305, respectively). Median overall survival (OS) was significantly longer in patients without ERCC1 expression (P = 0.0396). TS or GSTP1 expression were not related to survival (P = 0.4578, P = 0.8121, respectively). Multivariate analysis revealed that ERCC1 expression significantly impacted on OS (hazard ratio 1.92, P = 0.037). Conclusion: Immunohistochemical studies for ERCC1 may be useful in prediction of the clinical outcome in advanced gastric cancer patients treated with 5-FU and oxaliplatin.
Studies of attention and working memory address the fundamental limits in our ability to encode and maintain behaviorally relevant information, processes that are critical for goal-driven processing. ...Here we review our current understanding of the interactions between these processes, with a focus on how each construct encompasses a variety of dissociable phenomena. Attention facilitates target processing during both perceptual and postperceptual stages of processing, and functionally dissociated processes have been implicated in the maintenance of different kinds of information in working memory. Thus, although it is clear that these processes are closely intertwined, the nature of these interactions depends upon the specific variety of attention or working memory that is considered.
The advanced molybdenum-based rare process experiment (AMoRE) aims to search for neutrinoless double beta decay (
0
ν
β
β
) of
100
Mo with
∼
100
kg
of
100
Mo-enriched molybdenum embedded in cryogenic ...detectors with a dual heat and light readout. At the current, pilot stage of the AMoRE project we employ six calcium molybdate crystals with a total mass of 1.9 kg, produced from
48
Ca-depleted calcium and
100
Mo-enriched molybdenum (
48
depl
Ca
100
MoO
4
). The simultaneous detection of heat (phonon) and scintillation (photon) signals is realized with high resolution metallic magnetic calorimeter sensors that operate at milli-Kelvin temperatures. This stage of the project is carried out in the Yangyang underground laboratory at a depth of 700 m. We report first results from the AMoRE-Pilot
0
ν
β
β
search with a 111 kg day live exposure of
48
depl
Ca
100
MoO
4
crystals. No evidence for
0
ν
β
β
decay of
100
Mo is found, and a upper limit is set for the half-life of
0
ν
β
β
of
100
Mo of
T
1
/
2
0
ν
>
9.5
×
10
22
years
at 90% C.L. This limit corresponds to an effective Majorana neutrino mass limit in the range
⟨
m
β
β
⟩
≤
(
1.2
-
2.1
)
eV
.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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