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2.
Insect Mol Biol ; 28(3): 444-454, 2019 06.
Article in English | MEDLINE | ID: mdl-30582233

ABSTRACT

Developmental growth is an intricate process involving the coordinated regulation of the expression of various genes, and microRNAs (miRNAs) play crucial roles in diverse processes throughout animal development. The ecdysone-responsive miRNA, miR-252, is normally upregulated during the pupal and adult stages of Drosophila development. Here, we found that overexpression of miR-252 in the larval fat body decreased total tissue mass through a reduction in both cell size and cell number, causing a concomitant decrease in larval size. Furthermore, miR-252 overexpression led to a delayed larval-to-pupal transition with defective anterior spiracle eversion, as well as a decrease in adult size and mass. Conversely, adult flies lacking miR-252 showed an increase in mass compared with control flies. We found that miR-252 directly targeted mbt, encoding a p21-activated kinase, to repress its expression. Notably, co-overexpression of mbt rescued the developmental and growth defects associated with miR-252 overexpression, indicating that mbt is a biologically relevant target of miR-252. Overall, our data support a role for the ecdysone/miR-252/mbt regulatory axis in growth control during Drosophila development.


Subject(s)
Drosophila Proteins/genetics , Drosophila/genetics , Ecdysone/metabolism , MicroRNAs/metabolism , Protein Kinases/genetics , Animals , Drosophila/growth & development , Drosophila/metabolism , Drosophila Proteins/metabolism , Gene Expression Regulation, Developmental/physiology , Larva/genetics , Larva/growth & development , Larva/metabolism , Protein Kinases/metabolism , Signal Transduction/physiology
3.
Nature ; 545(7652): 71-74, 2017 05 04.
Article in English | MEDLINE | ID: mdl-28405018

ABSTRACT

The ability to control electronic states at the nanoscale has contributed to our modern understanding of condensed matter. In particular, quantum dot circuits represent model systems for the study of strong electronic correlations, epitomized by the Kondo effect. We use circuit quantum electrodynamics architectures to study the internal degrees of freedom of this many-body phenomenon. Specifically, we couple a quantum dot to a high-quality-factor microwave cavity to measure with exceptional sensitivity the dot's electronic compressibility, that is, its ability to accommodate charges. Because electronic compressibility corresponds solely to the charge response of the electronic system, it is not equivalent to the conductance, which generally involves other degrees of freedom such as spin. Here, by performing dual conductance and compressibility measurements in the Kondo regime, we uncover directly the charge dynamics of this peculiar mechanism of electron transfer. The Kondo resonance, visible in transport measurements, is found to be 'transparent' to microwave photons trapped in the high-quality cavity, thereby revealing that (in such a many-body resonance) finite conduction is achieved from a charge frozen by Coulomb interaction. This freezing of charge dynamics is in contrast to the physics of a free electron gas. We anticipate that the tools of cavity quantum electrodynamics could be used in other types of mesoscopic circuits with many-body correlations, providing a model system in which to perform quantum simulation of fermion-boson problems.

4.
J Nutr Health Aging ; 20(8): 816-824, 2016.
Article in English | MEDLINE | ID: mdl-27709230

ABSTRACT

OBJECTIVE: We aimed to investigate the association between metabolic syndrome (MS) and hearing impairment (HI) using nationally representative data from Korean adults. DESIGN, SETTING AND PARTICIPANTS: A total of 16,799 subjects (≥19 years old; 7,170 men and 9,629 women) who underwent pure tone audiometry testing were included in the analysis. Data were obtained from the fifth Korea National Health and Nutrition Examination Survey (2010-2012). Subjects were divided into two groups according to the presence of MS. RESULTS: Among the subjects with MS, 47% had HI. Logistic regression analysis revealed that MS was not an independent risk factor for HI, although increased fasting plasma glucose (OR 1·4, 95% CI: 1·1-1·8) was independently associated with HI. In addition, older age, male sex, very low body mass index (≤17·5 kg/m2), lower education level, smoking history, and occupational noise exposure were independently associated with HI. For low-frequency HI, independent risk factors included older age, lower educational level, lower economic status, and very low BMI (≤17·5 kg/m2). For high-frequency HI, independent risk factors included older age, male sex, lower educational level, lower economic status, increased blood pressure, lower high-density lipoprotein cholesterol, and smoking history. CONCLUSIONS: MS itself was not an independent risk factor for HI, and, among the individual metabolic components, only increased fasting plasma glucose was independently associated with HI.


Subject(s)
Glucose/metabolism , Hearing Loss/etiology , Metabolic Syndrome/complications , Adult , Aged , Aged, 80 and over , Fasting , Female , Glucose/analysis , Humans , Male , Middle Aged , Risk Factors , Young Adult
5.
Rev Sci Instrum ; 87(4): 046106, 2016 04.
Article in English | MEDLINE | ID: mdl-27131722

ABSTRACT

In this investigation, two near infrared (NIR) interferometric techniques for silicon wafer metrology are described and verified with experimental results. Based on the transparent characteristic of NIR light to a silicon wafer, the fiber based spectrally resolved interferometry can measure the optical thickness of the wafer and stitching low coherence scanning interferometry can reconstruct entire surfaces of the wafer.

6.
Int J Obes (Lond) ; 40(9): 1452-60, 2016 09.
Article in English | MEDLINE | ID: mdl-27146467

ABSTRACT

OBJECTIVES: The aim of this study was to explore the phenotypic differences underpinning obesity susceptibility or resistance based on the metabolic and transcriptional profiling of C57BL/6J mice fed a high-fat diet (HFD). METHODS: The mice were fed either a normal diet or HFD for 12 weeks. After 6 weeks, the mice on HFD were classified as either obesity-prone (OP) or obesity-resistant (OR) depending on the body weight gain. RESULTS: Lipid profiles from plasma and liver significantly improved in OR mice relative to the OP group. Energy expenditure was greater in OR mice than in OP mice, with a simultaneous decrease in body fat mass. Epididymal white adipose tissue (eWAT) and liver were enlarged in OP mice (with visible immune-cell infiltration), but these effects were attenuated in OR mice compared with OP mice. Overall glucose metabolism was enhanced in OR mice compared with OP mice, including homeostasis model assessment for insulin resistance, plasma glucose and insulin concentrations, glucokinase activity and hepatic glycogen. Plasma adipokines and proinflammatory cytokines were upregulated in OP mice, and these changes were attenuated in OR mice. Transcriptomic profiles of eWAT and liver revealed common and divergent patterns of transcriptional changes in OP and OR mice, and pointed to differential metabolic phenotypes of OP and OR mice. There were substantial differences between OP and OR mice in molecular pathways, including atherosclerosis signaling, sperm motility, cAMP-mediated signaling in eWAT; and fibrosis, agranulocyte adhesion and diapedesis, and atherosclerosis signaling in liver. CONCLUSIONS: Taken altogether, the results provide robust evidence of major divergence in the transcriptomes, phenotypes and metabolic processes between obesity susceptibility and obesity resistance in the HFD-fed C57BL/6J mice.


Subject(s)
Diet, High-Fat , Genetic Predisposition to Disease/genetics , Obesity/genetics , Obesity/metabolism , Phenotype , Transcriptome , Adipose Tissue, White/metabolism , Animals , Coronary Artery Disease/genetics , Disease Models, Animal , Energy Metabolism , Insulin Resistance/genetics , Liver/metabolism , Male , Mice , Mice, Inbred C57BL , RNA, Messenger/genetics , Weight Gain
7.
Int J Obes (Lond) ; 40(2): 338-45, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26268884

ABSTRACT

BACKGROUND: It is well known that high-fat diet (HFD) can cause immune system-related pathological alterations after a significant body weight gain. The mechanisms of the delayed pathological alterations during the development of diet-induced obesity (DIO) are not fully understood. METHODS: To elucidate the mechanisms underlying DIO development, we analyzed time-course microarray data obtained from a previous study. First, differentially expressed genes (DEGs) were identified at each time point by comparing the hepatic transcriptome of mice fed HFD with that of mice fed normal diet. Next, we clustered the union of DEGs and identified annotations related to each cluster. Finally, we constructed an 'integrated obesity-associated gene regulatory network (GRN) in murine liver'. We analyzed the epididymal white adipose tissue (eWAT) transcriptome usig the same procedure. RESULTS: Based on time-course microarray data, we found that the genes associated with immune responses were upregulated with an oscillating expression pattern between weeks 2 and 8, relatively downregulated between weeks 12 and 16, and eventually upregulated after week 20 in the liver of the mice fed HFD. The genes associated with immune responses were also upregulated at late stage, in the eWAT of the mice fed HFD. These results suggested that a critical transition occurred in the immune system-related transcriptomes of the liver and eWAT around week 16 of the DIO development, and this may be associated with the delayed pathological alterations. The GRN analysis suggested that Maff may be a key transcription factor for the immune system-related critical transition thatoccurred at week 16. We found that transcription factors associated with immune responses were centrally located in the integrated obesity-associated GRN in the liver. CONCLUSIONS: In this study, systems analysis identified regulatory network modules underlying the delayed immune system-related pathological changes during the development of DIO and could suggest possible therapeutic targets.


Subject(s)
Adaptive Immunity/genetics , Adipose Tissue, White/pathology , Liver/pathology , Obesity/metabolism , Adipose Tissue, White/metabolism , Animals , Diet, High-Fat , Disease Models, Animal , Gene Expression Profiling , Gene Regulatory Networks , Insulin Resistance , Lipid Metabolism/immunology , Liver/metabolism , Mice , Mice, Inbred C57BL , Obesity/immunology , Transcriptome , Up-Regulation
8.
J Viral Hepat ; 22 Suppl 4: 21-41, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26513446

ABSTRACT

The total number, morbidity and mortality attributed to viraemic hepatitis C virus (HCV) infections change over time making it difficult to compare reported estimates from different years. Models were developed for 15 countries to quantify and characterize the viraemic population and forecast the changes in the infected population and the corresponding disease burden from 2014 to 2030. With the exception of Iceland, Iran, Latvia and Pakistan, the total number of viraemic HCV infections is expected to decline from 2014 to 2030, but the associated morbidity and mortality are expected to increase in all countries except for Japan and South Korea. In the latter two countries, mortality due to an ageing population will drive down prevalence, morbidity and mortality. On the other hand, both countries have already experienced a rapid increase in HCV-related mortality and morbidity. HCV-related morbidity and mortality are projected to increase between 2014 and 2030 in all other countries as result of an ageing HCV-infected population. Thus, although the total number of HCV countries is expected to decline in most countries studied, the associated disease burden is expected to increase. The current treatment paradigm is inadequate if large reductions in HCV-related morbidity and mortality are to be achieved.


Subject(s)
Hepacivirus/isolation & purification , Hepatitis C, Chronic/epidemiology , Hepatitis C, Chronic/virology , Models, Statistical , Viremia/epidemiology , Viremia/virology , Adolescent , Adult , Aged , Aged, 80 and over , Cost of Illness , Female , Global Health , Hepatitis C, Chronic/mortality , Hepatitis C, Chronic/therapy , Humans , Incidence , Male , Middle Aged , Prevalence , Survival Analysis , Viremia/mortality , Viremia/therapy , Young Adult
9.
J Viral Hepat ; 22 Suppl 4: 42-65, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26513447

ABSTRACT

The hepatitis C virus (HCV) epidemic was forecasted through 2030 for 15 countries in Europe, the Middle East and Asia, and the relative impact of two scenarios was considered: increased treatment efficacy while holding the annual number of treated patients constant and increased treatment efficacy and an increased annual number of treated patients. Increasing levels of diagnosis and treatment, in combination with improved treatment efficacy, were critical for achieving substantial reductions in disease burden. A 90% reduction in total HCV infections within 15 years is feasible in most countries studied, but it required a coordinated effort to introduce harm reduction programmes to reduce new infections, screening to identify those already infected and treatment with high cure rate therapies. This suggests that increased capacity for screening and treatment will be critical in many countries. Birth cohort screening is a helpful tool for maximizing resources. Among European countries, the majority of patients were born between 1940 and 1985. A wider range of birth cohorts was seen in the Middle East and Asia (between 1925 and 1995).


Subject(s)
Communicable Disease Control/methods , Hepatitis C, Chronic/epidemiology , Hepatitis C, Chronic/prevention & control , Models, Statistical , Adolescent , Adult , Aged , Aged, 80 and over , Antiviral Agents/therapeutic use , Asia/epidemiology , Child , Child, Preschool , Diagnostic Tests, Routine/methods , Diagnostic Tests, Routine/statistics & numerical data , Drug Utilization , Europe/epidemiology , Female , Hepatitis C, Chronic/diagnosis , Hepatitis C, Chronic/therapy , Humans , Incidence , Infant , Infant, Newborn , Liver Transplantation , Male , Middle Aged , Middle East/epidemiology , Prevalence , Young Adult
10.
J Viral Hepat ; 22 Suppl 4: 4-20, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26513445

ABSTRACT

Detailed, country-specific epidemiological data are needed to characterize the burden of chronic hepatitis C virus (HCV) infection around the world. With new treatment options available, policy makers and public health officials must reconsider national strategies for infection control. In this study of 15 countries, published and unpublished data on HCV prevalence, viraemia, genotype, age and gender distribution, liver transplants and diagnosis and treatment rates were gathered from the literature and validated by expert consensus in each country. Viraemic prevalence in this study ranged from 0.2% in Iran and Lebanon to 4.2% in Pakistan. The largest viraemic populations were in Pakistan (7 001 000 cases) and Indonesia (3 187 000 cases). Injection drug use (IDU) and a historically unsafe blood supply were major risk factors in most countries. Diagnosis, treatment and liver transplant rates varied widely between countries. However, comparison across countries was difficult as the number of cases changes over time. Access to reliable data on measures such as these is critical for the development of future strategies to manage the disease burden.


Subject(s)
Hepacivirus/isolation & purification , Hepatitis C, Chronic/epidemiology , Hepatitis C, Chronic/virology , Adolescent , Adult , Aged , Aged, 80 and over , Antiviral Agents/therapeutic use , Child , Child, Preschool , Female , Genotype , Global Health , Hepacivirus/classification , Hepatitis C, Chronic/diagnosis , Hepatitis C, Chronic/therapy , Humans , Infant , Infant, Newborn , Liver Transplantation , Male , Middle Aged , Prevalence , Young Adult
11.
Int J Obes (Lond) ; 39(9): 1349-58, 2015 Sep.
Article in English | MEDLINE | ID: mdl-25920776

ABSTRACT

BACKGROUND: Galectin 1 (GAL1), an animal lectin is well characterized in the context of cancer, tumor environment, but its physiological roles in obesity remain to be demonstrated. In this study, we investigated whether targeted inhibition of GAL1 prevents obesity based on the previous observations that GAL1 is highly expressed in adipose tissues of high-fat diet (HFD)-induced obese rats. METHODS: Lipogenic capacity of Lgals1 knocked down adipocytes was evaluated by determining the expression levels of major lipogenic markers using real-time PCR and immunoblot analysis. GAL1 partner proteins were identified using co-immunoprecipitation followed by protein mass fingerprinting. Finally, inhibitory effect of GAL1 by thiodigalactoside (TDG) was assessed in adipocytes and HFD-induced obese rats. RESULTS: Knockdown of GAL1-encoding gene (Lgals1) attenuated adipogenesis and lipogenesis in both 3T3-L1 and HIB1B adipocytes. Further, direct treatment with TDG, a potent inhibitor of GAL1, to cultured adipocytes in vitro significantly reduced fat accumulation. Our animal experiment revealed that intraperitoneal injection of TDG (5 mg kg(-1)) once per week for 5 weeks in Sprague-Dawley (SD) rats resulted in dramatic inhibition of HFD-induced body weight gain (27.3% reduction compared with HFD-fed controls) by inhibiting adipogenesis and lipogensis as well as by increasing expression of the proteins associated with thermogenesis and energy expenditure. CONCLUSION: GAL1 has an essential role in HFD-induced obesity development. From a clinical viewpoint, pharmaceutical targeting of GAL1 using TDG and other inhibitor compounds would be a novel therapeutic approach for the treatment of obesity.


Subject(s)
Anti-Obesity Agents/pharmacology , Galectin 1/antagonists & inhibitors , Galectin 1/metabolism , Obesity/prevention & control , Thiogalactosides/pharmacology , Weight Gain/drug effects , 3T3-L1 Cells , Adipogenesis/drug effects , Adipose Tissue/drug effects , Adipose Tissue/metabolism , Animals , Diet, High-Fat , Disease Models, Animal , Immunoblotting , Lipogenesis/drug effects , Male , Mice , Obesity/etiology , Obesity/metabolism , PPAR gamma/metabolism , Rats , Rats, Sprague-Dawley , Real-Time Polymerase Chain Reaction , Thermogenesis/drug effects
12.
J Viral Hepat ; 22(6): 539-50, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25377516

ABSTRACT

It is unclear whether the reactivation of hepatitis B virus (HBV) influences the prognosis of hepatocellular carcinoma (HCC) after resection in patients with chronic hepatitis B. The aim of this study was to identify the influence of HBV reactivation on the recurrence of hepatitis B-related HCC after curative resection in patients with low viral load (HBV DNA <2000 IU/mL). We retrospectively analysed a total of 130 patients who underwent curative resection for HBV-related early stage HCC (single nodule; <5 cm/two or three nodules; <3 cm) with pre-operative HBV DNA levels <2000 IU/mL with serial HBV DNA tests. The predictive factors including HBV reactivation for the recurrence of HBV-related HCC after curative resection were investigated. Fifty-three patients (41%) had HBV reactivation after resection among 130 patients. HBV reactivation was observed in 22 of 53 patients with undetectable baseline HBV DNA and in 31 of 77 patients with detectable baseline HBV DNA. Cumulative recurrence rates after resection at 1, 2 and 3 years were 17.0%, 23.3% and 31.4%, respectively. The multivariable analysis demonstrated that the risk factors for the recurrence were the presence of microvascular invasion (hazard ratio (HR) 2.62, P = 0.003), multinodularity (HR 4.61, P = 0.005), HBV reactivation after resection (HR 2.03, P = 0.032) and HBeAg positivity (HR 2.06, P = 0.044). HBV reactivation after curative resection is associated with the recurrence of HBV-related HCC in patients with low viral load.


Subject(s)
Carcinoma, Hepatocellular/etiology , Carcinoma, Hepatocellular/surgery , Hepatitis B virus/physiology , Hepatitis B, Chronic/complications , Hepatitis B, Chronic/virology , Liver Neoplasms/etiology , Liver Neoplasms/surgery , Viral Load , Virus Activation , Adult , Aged , Carcinoma, Hepatocellular/pathology , Female , Hepatitis B, Chronic/drug therapy , Humans , Liver Cirrhosis/etiology , Liver Cirrhosis/pathology , Liver Neoplasms/pathology , Male , Middle Aged , Neoplasm Grading , Neoplasm Recurrence, Local , Neoplasm Staging , Postoperative Period , Preoperative Period , Risk Factors , Treatment Outcome , Tumor Burden
13.
Aliment Pharmacol Ther ; 40(6): 695-704, 2014 Sep.
Article in English | MEDLINE | ID: mdl-25078671

ABSTRACT

BACKGROUND: The risk of spontaneous bacterial peritonitis (SBP) associated with proton pump inhibitor (PPI) use has been raised in cirrhotic patients with ascites. However, this is based on case-control studies, often with a small series. AIM: To determine whether PPI use increases the risk of SBP using a large cohort. METHODS: This retrospective cohort study included 1965 cirrhotic patients with ascites diagnosed between January 2005 and December 2009. The SBP incidence rate was compared between the PPI and non-PPI groups before and after propensity score matching to reduce the effect of selection bias and potential confounders. Multivariate analysis was conducted to confirm the association of PPI use with SBP. RESULTS: After excluding 411 patients, 1554 were analysed. Among them, 512 patients (32.9%) were included in the PPI group. The annual SBP incidence rate was higher in the PPI group than in the non-PPI group (10.6% and 5.8%, P = 0.002) before matching. Indications for PPI use and dose of PPI were similar between patients with and without SBP. In the propensity score matched cohort (402 pairs), the SBP incidence rate was also higher in the PPI group than in the non-PPI group (10.8% vs. 6.0%, P = 0.038). Multivariate analysis revealed that PPI use (Hazard ratio 1.396; 95% confidence interval, 1.057-1.843; P = 0.019) was the independent risk factor for SBP. CONCLUSIONS: Proton pump inhibitor use significantly increases the risk of spontaneous bacterial peritonitis in cirrhotic patients with ascites. Proton pump inhibitor use should be undertaken with greater caution and appropriately in patients with cirrhosis.


Subject(s)
Ascites/complications , Bacterial Infections/complications , Liver Cirrhosis/complications , Peritonitis/complications , Proton Pump Inhibitors/adverse effects , Aged , Ascites/epidemiology , Bacterial Infections/epidemiology , Female , Humans , Liver Cirrhosis/epidemiology , Male , Middle Aged , Peritonitis/epidemiology , Propensity Score , Retrospective Studies
14.
Cell Death Dis ; 5: e1345, 2014 Jul 17.
Article in English | MEDLINE | ID: mdl-25032868

ABSTRACT

Mesenchymal stem cells (MSCs) possess immunomodulatory activities, including suppression of T- and B-cell activation. However, their effects on atopic dermatitis (AD) have not yet been studied. Using an ovalbumin-induced AD mouse model, we investigated whether MSCs can be used as therapeutics in AD. We isolated both allogeneic and syngeneic clonal MSCs (cMSCs) from mouse bone marrow according to the subfractionation culturing method. Our cMSCs suppressed both T- and B-cell activation. T-cell proliferation and cytokine production, including interferon (IFN)-γ and interleukin (IL)-4, were suppressed by inhibition of transcription factors, such as T-bet, GATA-3, and c-Maf. Those transcription factors were nitric oxide dependent. Immunoglobulin E (IgE) suppression occurred through downregulation of AID and BLIMP-1, important regulators for isotype class switch and B-cell differentiation. The cMSCs were injected intravenously into ovalbumin-induced AD mouse model, and the therapeutic effects were analyzed. Injection of both allogeneic and syngeneic cMSCs in an AD mouse model inhibited cell infiltration in skin lesions and decreased the serum level of IgE. IL-4 expression was also suppressed by cMSCs in both the lymph node and skin. The cMSCs migrated to skin lesions and draining lymph nodes. Taken together, these data demonstrated that cMSCs, which suppressed T- and B-cell functions, can be used for the treatment of AD in mice.


Subject(s)
Bone Marrow Cells/cytology , Cell Differentiation , Cell- and Tissue-Based Therapy , Dermatitis, Atopic/therapy , Mesenchymal Stem Cell Transplantation , Animals , B-Lymphocytes/immunology , Cytokines/immunology , Dermatitis, Atopic/chemically induced , Dermatitis, Atopic/immunology , Disease Models, Animal , Humans , Mesenchymal Stem Cells/cytology , Mice , Mice, Inbred BALB C , Mice, Inbred C3H , Ovalbumin/adverse effects , T-Lymphocytes/immunology
15.
Clin Biochem ; 47(6): 489-93, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24503006

ABSTRACT

OBJECTIVES: This study was performed to establish the reference intervals for whole blood viscosity (WBV) using the analytical performance-evaluated scanning capillary tube viscometer (SCTV). DESIGN AND METHODS: The analytical performance of the SCTV was evaluated using three different levels of QC materials and sixty human EDTA-blood samples. To establish the reference intervals for WBV, 297 healthy individuals (123 men and 174 women) were selected from 1083 subjects. RESULTS: Within-day precisions with QC materials and human whole blood and between-day precisions with QC materials were below 5.0%, 6.6% and 8.0% in CVs at all shear rates, respectively. Comparison tests between the SCTV and the Brookfield viscometer showed a significant correlation (R(2)=0.972, p<0.001). The reference intervals for WBV in healthy men were 3.66-5.41cP at 300s(-1) and 23.15-36.45cP at 1s(-1) while those in women were 3.27-4.32cP at 300s(-1) and 18.20-27.36cP at 1s(-1), respectively. CONCLUSIONS: Using the analytical performance-evaluated SCTV, the reference intervals for WBV were established in healthy adults, which could be beneficial to the clinical utility of WBV in the aspect of appropriate modalities for the improvement of blood viscosity.


Subject(s)
Blood Specimen Collection/instrumentation , Blood Specimen Collection/methods , Blood Viscosity/physiology , Adult , Female , Humans , Male , Quality Control , Reference Values
16.
Int J Obes (Lond) ; 38(8): 1075-82, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24281650

ABSTRACT

BACKGROUND: 4-1BB, a member of the TNF receptor superfamily, has a role in various inflammatory pathologies through its interaction with 4-1BB ligand. We previously demonstrated that it participates in initiating and promoting obesity-induced adipose inflammation in a rodent model. OBJECTIVE: In this study, we examined whether 4-1BB is related to obesity-induced adipose inflammation and metabolic parameters in humans. METHODS: A total of 50 subjects, 25 obese (body mass index (BMI)≥25 kg m(-2)) and 25 lean (BMI<23 kg m(-2)) participated in the study. The levels of 4-1BB transcripts and soluble 4-1BB protein (s4-1BB) in subcutaneous adipose tissue were measured by quantitative real-time PCR and enzyme-linked immunosorbent assay, respectively. Inflammatory and metabolic parameters were measured by enzymatic analysis and immunoassay. RESULTS: Obese subjects had higher levels of both 4-1BB transcripts and s4-1BB protein in subcutaneous adipose tissue than lean controls, and the levels were correlated with BMI and the expression of inflammatory markers, as well as with serum metabolic parameters. Moreover, s4-1BB was released from human adipocytes, and elicited chemotactic responses from human monocytes/T cells as well as enhancing their inflammatory activity, indicating that it may promote human adipose inflammation. DISCUSSION: Our data demonstrate that elevated levels of 4-1BB transcripts and s4-1BB in adipose tissue are closely associated with obesity-induced inflammation and metabolic dysregulation. They suggest that both 4-1BB transcripts and s4-1BB could serve as novel biomarkers and/or therapeutic targets for obesity-induced inflammation and metabolic syndrome in humans.


Subject(s)
4-1BB Ligand/metabolism , Adipocytes/metabolism , Adipose Tissue/metabolism , Inflammation/metabolism , Obesity/metabolism , Tumor Necrosis Factor Receptor Superfamily, Member 9/metabolism , Adipose Tissue/immunology , Body Mass Index , Cells, Cultured , Enzyme-Linked Immunosorbent Assay , Female , Humans , Inflammation/immunology , Male , Obesity/immunology , Obesity/physiopathology , Real-Time Polymerase Chain Reaction , Solubility
17.
Int J Obes (Lond) ; 37(12): 1524-31, 2013 Dec.
Article in English | MEDLINE | ID: mdl-23628853

ABSTRACT

OBJECTIVE: The aim of this study was to establish the time-course of molecular events in intrascapular brown adipose tissue (iBAT) during the development of diet-induced obesity using microarrays and molecular network analysis. DESIGN: C57BL/6J male inbred mice were fed a high-fat diet (HFD) or normal diet (ND) and killed at multiple time-points over 24 weeks. METHODS: Global transcriptional changes in iBAT were determined by time-course microarrays of pooled RNA (n=6, pools per time-point) at 2, 4, 8, 20 and 24 weeks using Illumina MouseWG-6 v2.0 Beadchips. Molecular networks were constructed using the Ingenuity knowledgebase based on differentially expressed genes at each time-point. RESULTS: Body weight and subcutaneous adipose were progressively increased over 24 weeks, whereas iBAT was significantly increased between 6 and 12 weeks in HFD-fed C57BL/6J mice compared with controls. Blood glucose and insulin levels were increased between 16 and 24 weeks. Time-course microarrays, revealed 155 differentially expressed genes at one or more time-points over 24 weeks in the iBAT of HFD-fed mice compared with controls. Time-course network analysis revealed a network of skeletal muscle development genes that was activated between 2 and 4 weeks, subsequently a network of immune trafficking genes was activated at 8 weeks. After 20 and 24 weeks, multiple lipid metabolism and immune response networks were activated. Several target genes identified by time-course microarrays were independently validated using RT-qPCR. Tnnc1 was upregulated early between 2 and 4 weeks, later Cd68 and Col1a1 were upregulated between 20 and 24 weeks, whereas 11ß-hydroxysteroid dehydrogenase (Hsd11b1) was consistently downregulated during the development of diet-induced obesity. CONCLUSION: Molecular networks in iBAT are modulated in a time-dependent manner in response to a HFD. A broad range of gene targets exists to alter molecular changes within iBAT during the development of diet-induced obesity.


Subject(s)
Adaptive Immunity/genetics , Adipose Tissue, Brown/pathology , Antigens, CD/metabolism , Antigens, Differentiation, Myelomonocytic/metabolism , Gene Regulatory Networks , Lipid Metabolism/immunology , Obesity/metabolism , 11-beta-Hydroxysteroid Dehydrogenase Type 1/metabolism , Adipose Tissue, Brown/immunology , Animals , Collagen Type I/metabolism , Collagen Type I, alpha 1 Chain , Diet, High-Fat , Down-Regulation , Gene Expression Profiling , Insulin Resistance/immunology , Male , Mice , Mice, Inbred C57BL , Obesity/etiology , Obesity/genetics , Obesity/immunology , Tenascin/metabolism , Time Factors , Up-Regulation
18.
Transplant Proc ; 44(2): 403-8, 2012 Mar.
Article in English | MEDLINE | ID: mdl-22410028

ABSTRACT

BACKGROUND: Many patients are diagnosed with hepatocellular carcinoma (HCC) within the Milan criteria. In Korea, these patients are preferentially treated with locoregional therapy (LRT) instead of living donor liver transplantation. We investigated the effectiveness of LRT in liver transplant recipients who met the Milan criteria at the time of HCC diagnosis and investigated risk factors for HCC recurrence. METHODS: We retrospectively reviewed the medical records of patients diagnosed with HCC who met the Milan criteria between 2002 and 2008. RESULTS: We performed 101 liver transplants for HCC during the study period. Seventy-one patients (70%) underwent pretransplant LRT. The disease-free survival rates at 1, 3, and 5 years in patients who received LRT were 96.6%, 93.1%, and 93.1%, and in those who did not receive LRT, 94.2%, 83.4%, and 83.4%, respectively. There were no differences between the 2 groups. Multivariate analysis showed that a low Model for End-Stage Liver Disease (MELD) score and microvascular invasion were independent predictors of HCC recurrence after transplantation. The MELD scores and rate of microvascular invasion were not statistically different in patients with or without previous LRT. CONCLUSION: Pretransplant LRT for patients with HCC who met the Milan criteria at the time of diagnosis did not provide a clear benefit with respect to HCC recurrence after transplantation. If patients have suitable living donors, those who meet the Milan criteria should undergo a liver transplantation as soon as possible.


Subject(s)
Carcinoma, Hepatocellular/therapy , Catheter Ablation , Chemoembolization, Therapeutic , Ethanol/administration & dosage , Hepatectomy , Liver Neoplasms/therapy , Liver Transplantation , Living Donors , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/surgery , Catheter Ablation/adverse effects , Catheter Ablation/mortality , Chemoembolization, Therapeutic/adverse effects , Chemoembolization, Therapeutic/mortality , Chemotherapy, Adjuvant , Disease Progression , Disease-Free Survival , Ethanol/adverse effects , Female , Hepatectomy/adverse effects , Hepatectomy/mortality , Humans , Injections , Kaplan-Meier Estimate , Liver Neoplasms/drug therapy , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Liver Neoplasms/surgery , Liver Transplantation/adverse effects , Liver Transplantation/mortality , Logistic Models , Male , Middle Aged , Multivariate Analysis , Neoadjuvant Therapy , Neoplasm Recurrence, Local , Proportional Hazards Models , Republic of Korea , Retrospective Studies , Risk Assessment , Risk Factors , Time Factors , Treatment Outcome , Tumor Burden
19.
Asian-Australas J Anim Sci ; 25(11): 1540-5, 2012 Nov.
Article in English | MEDLINE | ID: mdl-25049514

ABSTRACT

Steroidogenesis requires coordination of the anabolic and catabolic pathways of lipid metabolism, but the profile of proteins associated with progesterone synthesis in cyclic and pregnant corpus luteum (CL) is not well-known in cattle. In Experiment 1, plasma progesterone level was monitored in cyclic cows (n = 5) and pregnant cows (n = 6; until d-90). A significant decline in the plasma progesterone level occurred at d-19 of cyclic cows. Progesterone level in abbatoir-derived luteal tissues was also determined at d 1 to 5, 6 to 13 and 14 to 20 of cyclic cows, and d-60 and -90 of pregnant cows (n = 5 each). Progesterone level in d-60 CL was not different from those in d 6 to 13 CL and d-90 CL, although the difference between d 6 to 13 and d-90 was significant. In Experiment 2, protein expression pattern in CL at d-90 (n = 4) was compared with that in CL of cyclic cows at d 6 to 13 (n = 5). Significant changes in the level of protein expression were detected in 32 protein spots by two-dimensional polyacrylamide gel electrophoresis (2-DE), and 23 of them were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Six proteins were found only in pregnant CL, while the other 17 proteins were found only in cyclic CL. Among the above 6 proteins, vimentin which is involved in the regulation of post-implantation development was included. Thus, the protein expression pattern in CL was disorientated from cyclic luteal phase to mid pregnancy, and alterations in specific CL protein expression may contribute to the maintenance of pregnancy in Korean native cows.

20.
Curr Mol Med ; 11(4): 304-16, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21506921

ABSTRACT

Worldwide obesity is a growing health problem, associated with increased risk of chronic disease. Understanding the molecular basis of adipogenesis and fat cell development in obesity is essential to identify new biomarkers and therapeutic targets for the development of anti-obesity drugs. microRNAs (miRNAs) appear to play regulatory roles in many biological processes associated with obesity, including adipocyte differentiation, insulin action and fat metabolism. Recent studies show miRNAs are dysregulated in obese adipose tissue. During adipogenesis miRNAs can accelerate or inhibit adipocyte differentiation and hence regulate fat cell development. In addition miRNAs may regulate adipogenic lineage commitment in multipotent stem cells and hence govern fat cell numbers. Recent findings suggest miR-519d may be associated with human obesity, but larger case-control studies are needed. Few miRNA targets have been experimentally validated in adipocytes but interestingly both miR-27 and miR-519d target PPAR family members, which are well established regulators of fat cell development. In this review recent advances in our understanding of the role of miRNAs in fat cell development and obesity are discussed. The potential of miRNA based therapeutics targeting obesity is highlighted as well as recommendations for future research which could lead to a breakthrough in the treatment of obesity.


Subject(s)
Adipogenesis/genetics , Adipose Tissue/metabolism , MicroRNAs/metabolism , Obesity/metabolism , PPAR gamma/metabolism , Adipocytes/cytology , Adipocytes/metabolism , Adipose Tissue/cytology , Animals , Antagomirs , Anti-Obesity Agents/metabolism , Biomarkers/analysis , Cell Differentiation/drug effects , Cell Differentiation/genetics , Gene Expression Regulation/drug effects , Humans , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/metabolism , Mice , MicroRNAs/genetics , Molecular Targeted Therapy/methods , Multipotent Stem Cells/cytology , Multipotent Stem Cells/metabolism , Obesity/genetics , Oligonucleotides/metabolism , Oligonucleotides/pharmacology , PPAR gamma/genetics , Rats , Reverse Transcriptase Polymerase Chain Reaction
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