Objective
To compare the clinical effectiveness of two treatment strategies for active rheumatoid arthritis (RA) refractory to conventional synthetic disease-modifying anti-rheumatic drugs ...(csDMARDs): starting TNF inhibitors (TNFIs) or changing csDMARDs.
Methods
We used two nationwide Korean RA registries for patient selection. TNFI users were selected from the BIOPSY, which is an inception cohort of RA patients starting biologic DMARDs. As a control group, we selected RA patients with moderate or high disease activity from the KORONA database whose treatment was changed to other csDMARDs. After comparing baseline characteristics between the two groups in either unmatched or propensity score matched cohorts, we compared potential differences in the 1-year remission rate as a primary outcome and changes in HAQ-DI and EQ-5D scores as secondary outcomes.
Results
A total of 356 TNFI starters and 586 csDMARD changers were identified from each registry as unmatched cohorts, and 294 patients were included in the propensity score matched cohort. In the intention-to-treat analysis, TNFI starters had higher 1-year remission rates than csDMARD changers in both unmatched (19.1 vs. 18.4%,
p
< 0.01) and matched cohorts (19.7 vs. 15.0%,
p
< 0.01). In per protocol analysis, TNFI starters had much higher remission rates in unmatched (37.2 vs. 28.0%,
p
= 0.04) and matched cohorts (35.4 vs. 19.1%,
p
= 0.04). However, in matched cohorts, no significant differences were observed between two groups in HAQ-DI and EQ-5D scores.
Conclusions
We compared the clinical effectiveness of the two treatment strategies for active RA refractory to csDMARDs. TNFI starters showed higher 1-year remission rates than csDMARD changers.
Platelet derived growth factor (PDGF)-BB is one of the most potent vascular smooth muscle cell (VSMC) proliferative factors, and abnormal VSMC proliferation by PDGF-BB plays an important role in the ...development and progression of cardiovascular problems, including restenosis after coronary angioplasty and atherosclerosis. Previous phytochemical studies on the stems or root barks of Cudrania tricuspidata (Moraceae) resulted in the isolation of various isoprenylated xanthones and flavonoids, some of which have anti-cancer, hepatoprotective, anti-inflammatory and anti-oxidant activities. In the present study, we investigated the antiproliferative effect of cudratricusxanthone A isolated from the root bark of C. tricuspidata and its underlying mechanism in VSMCs. Antiproliferative effects of cudratricusxanthone A on VSMCs were examined by direct cell counting and 3H-thymidine incorporation assays. Cudratricusxanthone A inhibited 3H-thymidine incorporations into DNA in VSMCs that occurred in response to treatment with 50 ng/ml PDGF-BB. PDGF-BB-stimulated DNA synthesis was significantly reduced to 86.1, 80.2, 64.2 and 25.1% at concentrations of 0.1, 1, 2 and 3 μM, respectively. Moreover, pre-treatment with cudratricusxanthone A (0.1—3 μM) suppressed this PDGF-BB-stimulated cell number in a concentration-dependent manner. The inhibition percentages were 11.1, 22.7, 51.3 and 81.5% at the concentrations of 0.1, 1, 2 and 3 μM, respectively. We also investigated the mechanism of antiproliferative effects by cudratricusxanthone A in PDGF-BB-stimulated VSMCs. In Western blot analysis, 50 ng/ml PDGF-BB-stimulated phospholipase C (PLC)γ1, Ras, and extracellular signal-regulated kinase1/2 (ERK1/2) phosphorylations were inhibited by cudratricusxanthone A (0.1—3 μM). Consisted with these findings, cudratricusxanthone A inhibited PDGF-receptor β chain (PDGF-Rβ) phosphorylation induced by PDGF-BB in a concentration-dependent manner. These findings suggest that the inhibitory effects of cudratricusxanthone A on DNA synthesis and proliferation by PDGF-BB-stimulated VSMCs are mediated by the suppressions of the PDGF-Rβ and its downstream signaling pathways. Our observation may explain in part mechanistic basis for the prevention of cardiovascular diseases, such as atherosclerosis and restenosis after coronary angioplasty by cudratricusxanthone A.
Background
Element™ Auto‐coding Blood Glucose Monitoring System (BGMS; Infopia Co., Ltd., Anyang‐si, Korea) was developed for self‐monitoring of blood glucose (SMBG).
Methods
Precision, linearity, ...and interference were tested. Eighty‐four capillary blood samples measured by Element™ BGMS were compared with central laboratory method (CLM) results in venous serum. Accuracy was evaluated using ISO 15197:2013 criteria.
Results
Coefficients of variation (CVs; mean) were 2.4% (44.2 mg/dl), 3.7% (100.6 mg/dl), and 2.1% (259.8 mg/dl). Linearity was shown at concentrations 39.25–456.25 mg/l (y = 0.989 + 0.984x, SE = 17.63). Up to 15 mg/dl of galactose, ascorbic acid, and acetaminophen, interference > 10.4% was not observed. Element™ BGMS glucose was higher than CLM levels by 3.2 mg/dl (at 200 mg/dl) to 8.2 mg/dl (at 100 mg/dl). The minimum specification for bias (3.3%) was met at 140 and 200 mg/l glucose. In the Clarke and consensus error grids, 100% of specimens were within zone A and B. For Element™ BGMS values, 92.9% (78/84) to 94.0% (79/84) were within a 15 mg/dl (< 100 mg/dl) or 15% (> 100 mg/dl) of the average CLM value.
Conclusion
Element™ BGMS was considered an appropriate SMBG for home use; however, the positive bias at low‐to‐mid glucose levels requires further improvement.
Background: There have been lots of studies about the relationship between chronic use of alcohol and the development of type 2 diabetes mellitus (T2DM). Chronic use of alcohol can be affected by ...the altered level of ghrelin and leptin which regulate food‐seeking behavior having similar mechanism of controlling alcohol‐craving behavior. Those peptides are known to be correlated with T2DM. Ghrelin and leptin also have been regarded as possible regulators of glucose metabolism and insulin function. Hence, there is the possibility that ghrelin and leptin can be related with deteriorated pathophysiology of T2DM in alcoholic patients.
Methods: Patients with alcohol dependence diagnosed by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM‐IV‐TR) underwent an 75 g oral glucose‐tolerance test (OGTT), to classify them to normal glucose tolerance (NGT, n = 52), pre‐diabetes including impaired glucose tolerance (IGT), impaired fasting glucose level (IFG) and combination of IGT and IFG (Pre‐DM, n = 26) and T2DM (n = 24) groups. Fasting plasma ghrelin and leptin levels were compared among groups.
Results: There was no difference of ghrelin concentration among the groups but the leptin concentration was significantly different between NGT and T2DM group (p < 0.05). Increased leptin levels were significantly correlated with body mass index (BMI), insulin level, and insulin resistance.
Conclusions: Chronic alcohol drinking might produce leptin resistance which makes leptin significantly correlated with fasting insulin concentration and insulin resistance. Therefore, we suppose that increased level of leptin by chronic alcohol use could be one of the main mechanisms that develop insulin resistance in alcoholic patients.
The Madin-Darby canine kidney (MDCK) cell line is typically used to analyze pathological features after canine influenza virus (CIV) infection. However, MDCK cells are not the ideal cell type, ...because they are kidney epithelial cells. Therefore, we generated an immortalized canine tracheal epithelial cell line, KU-CBE, to more reliably study immune responses to CIV infection in the respiratory tract. KU-CBE cells expressed the influenza virus receptor, α-2,3-sialic acid (SA), but not α-2,6-SA. KU-CBE and MDCK cells infected with H3N2 CIV demonstrated comparable virus growth kinetics. Gene expression levels of interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor (TNF)-α, and interferon (IFN)-β were estimated in both KU-CBE and MDCK cells infected with CIV by real-time reverse transcription polymerase chain reaction (qRT-PCR). Of these cytokines, IL-4, IL-10, TNF-α, and IFN-β mRNAs were detected in both cell lines. Gene expression of IL-4, IL-10, and TNF-α was not significantly different in the two cell lines. However, MDCK cells exhibited a significantly higher level of IFN-β mRNA than KU-CBE cells at 18 h post infection. Additionally, the protein concentrations of these four cytokines were determined by enzyme-linked immunosorbent assay (ELISA) using cell culture supernatants obtained from the two CIV-infected cell lines. MDCK cells produced significantly higher amounts of IL-4 and IFN-β than KU-CBE cells. However, KU-CBE cells produced a significantly higher amount of TNF-α than MDCK cells. These data indicated that the newly developed canine tracheal epithelial cells exhibited different cytokine production patterns compared to MDCK cells when infected with CIV. Inflammation of the respiratory tract of dogs induced by CIV infection may be attributed to the elevated expression level of TNF-α in canine tracheal epithelial cells.
Leptin, a hormone with multiple biological actions, is produced predominantly by adipose tissue. Among its functions, leptin can stimulate tumour cell growth. Oestrogen receptor α (ERα), which plays ...an essential role in breast cancer development, can be transcriptionally activated in a ligand-independent manner. In this study, we investigated the effect of leptin on CYP1B1 expression and its mechanism in breast cancer cells. Leptin induced CYP1B1 protein, messenger RNA expression and promoter activity in ERα-positive MCF-7 cells but not in ERα-negative MDA-MB-231 cells. Additionally, leptin increased 4-hydroxyoestradiol in MCF-7 cells. Also, ERα knockdown by siRNA significantly blocked the induction of CYP1B1 expression by leptin, indicating that leptin induced CYP1B1 expression via an ERα-dependent mechanism. Transient transfection with CYP1B1 deletion promoter constructs revealed that the oestrogen response element (ERE) plays important role in the up-regulation of CYP1B1 by leptin. Furthermore, leptin stimulated phosphorylation of ERα at serine residues 118 and 167 and increased ERE-luciferase activity, indicating that leptin induced CYP1B1 expression by ERα activation. Finally, we found that leptin activated ERK and Akt signalling pathways, which are upstream kinases related to ERα phosphorylation induced by leptin. Taken together, our results indicate that leptin-induced CYP1B1 expression is mediated by ligand-independent activation of the ERα pathway as a result of the activation of ERK and Akt in MCF-7 cells.
•Leptin increased 4-hydroxyoestradiol in MCF-7 breast cancer cells.•Leptin activated ERK and Akt kinases related to ERα phosphorylation.•Leptin induces phosphorylation of ERα at serine residues 118 and 167.•Leptin induces ERE-luciferase activity.
Fibromyalgia syndrome (FMS) is characterized by widespread chronic musculoskeletal pain, stiffness and pressure hyperalgesia at soft tissue tender points. Patients with FMS may exhibit a tendency ...towards cold extremities and cold-induced vasospasm. Endothelin-1 (EDN1) is a potent vasoconstrictor that is mainly produced by endothelial cells. The present study aimed to determine whether plasma expression levels avvnd single-nucleotide polymorphism (SNP; rs1800541) of the EDN1 gene were associated with FMS and/or any of its clinical variables. Plasma EDN1 levels were assessed by ELISA, and SNP genotypes were determined using polymerase chain reaction-high-resolution melting curve analysis. Patients with the TG genotype and the G allele may have an elevated risk of FMS. In addition, patients with FMS with the TG genotype and/or T allele exhibited higher plasma EDN1 levels compared with healthy controls. EDN1 levels increased significantly in patients with FMS compared with normal controls. In addition, EDN1 SNP was found to be associated with susceptibility to FMS.
In the original publication of this article 1, the author wanted to correct the ‘XXX University Hospital’ in below two sentences. The ‘XXX University Hospital’ should be the ‘Hanyang University ...Hospital’.
•The natural reassortant H9N2 virus was isolated from wild bird in Korea.•The H9N2 isolate was North American–Eurasian reassortant virus.•All 8 genes were associated with Chinese H9N2 viruses ...isolated from wild birds.•International movement of the whole reassortant AIV was detected.
In 2011, we isolated a natural recombinant H9N2 avian influenza virus from fecal droppings of bean goose (Anser fabalis) in Korea. Phylogenetic analyses showed that the A/bean goose/Korea/220/2011(H9N2) isolate is a reassortant of Eurasian and North American lineages of avian influenza virus. In addition, the complete genome sequence, including all 8 gene segments, was associated with Chinese H9N2 viruses isolated from wild birds in the Hunan East Dongting Lake National Nature Reserve. These data provide direct evidence for the exchange of avian influenza viruses between Korea and China via wild birds.
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