Kaempferol inhibits IL‑1β‑induced proliferation of rheumatoid arthritis synovial fibroblasts and the production of COX‑2, PGE2 and MMPs

Inflammatory cytokines, matrix metalloproteinases (MMPs) and cyclooxygenase (COX)‑2 released from rheumatoid arthritis synovial fibroblasts (RASFs) are involved in the destruction of both articular bone and cartilage. Kaempferol has been reported to act as an antioxidant and anti‑inflammatory agent by inhibiting nitric oxide synthase and COX enzymes. The aim of the present study was to determine the effects of kaempferol on the interleukin‑1β (IL‑1β)‑induced proliferation of RASFs and the production of MMPs, COX and prostaglandin E2 (PGE2) by RASFs. The proliferation of the RASFs stimulated with IL‑1β and treated with/without kaempferol was evaluated by CCK‑8 assay. The expression of MMPs, TIMP metallopeptidase inhibitor‑1 (TIMP‑1), COXs, PGE2 and that of intracellular MAPK signaling molecules, including p‑ERK, p‑p38, p‑JNK and nuclear factor‑κB (NF‑κB) was examined by immunoblotting or semi‑quantitative reverse transcription‑polymerase chain reaction (RT‑PCR) and ELISA under the conditions described above. Kaempferol inhibited the proliferation of both unstimulated and IL‑1β‑stimulated RASFs, as well as the mRNA and protein expression of MMP‑1, MMP-3, COX‑2 and PGE2 induced by IL‑1β. Kaempferol also inhibited the phosphorylation of ERK‑1/2, p38 and JNK, as well as the activation of NF‑κB induced by IL‑1β. These results indicate that kaempferol inhibits synovial fibroblast proliferation, as well as the production of and MMPs, COX‑2 and PGE2, which is involved in articular inflammation and destruction in rheumatoid arthritis (RA). Our data suggest that kaempferol may be a novel therapeutic agent for the treatment of RA

Ethyl acetate fraction from Angelica sinensis inhibits IL-1β-induced rheumatoid synovial fibroblast proliferation and COX-2, PGE2, and MMPs production

BACKGROUND: The root of Angelica sinensis (AS), also known as "Dang-gui," was a popular herbal medicine widely used in the treatment of gynecological diseases in China, Korea, and Japan for a long time. This study aimed to determine the effects of ethyl acetate fraction from Angelica sinensis (EAAS) on the interleukin-1β (IL-1β)-induced proliferation of rheumatoid arthritis synovial fibroblasts (RASFs), and production of matrix metalloproteinases (MMPs), cyclooxygenase (COX) 2, and prostaglandin E2 (PGE2), involved in articular bone and cartilage destruction, by RASFs. RESULTS: RASF proliferation was evaluated with cholecystokinin octapeptide (CCK-8) reagent in the presence of IL-1β with/without EAAS. Expression of MMPs, tissue inhibitor of metalloproteinases-1 (TIMP-1), COXs, PGE2, and intracellular mitogen-activated protein kinase (MAPK) signaling molecules, including p-ERK, p-p38, p-JNK, and NF-κB, were examined using immunoblotting or semi-quantitative reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. EAAS inhibited IL-1β-induced RASF proliferation; MMP-1, MMP-3, and COX-2 mRNA and protein expressions; and PGE2 production. EAAS also inhibits the phosphorylation of ERK-1/2, p38, and JNK, and activation of NF-κB by IL-1β. CONCLUSION: EAAS might be a new therapeutic modality for rheumatoid arthritis management

Complete Atrioventricular Block in an Adolescent With Rheumatic Fever

Rheumatic fever is an acute inflammatory sequela following a group A, β-hemolytic streptococcal infection. Rheumatic fever is characterized by polyarthritis, carditis, chorea, subcutaneous nodules, and erythema marginatum as the major diagnostic criteria. Rarely, advanced heart block may also occur. A 13-year-old boy was admitted to the Pediatric Department for evaluation and management of complete atrioventricular block. The patient had exertional dyspnea for 1 month. Based on the findings of mitral regurgitation, fever, elevated acute phase reactants, and a high antistreptolysin O titer, the patient was diagnosed with rheumatic fever. A benzathine penicillin injection was administered, as well as salicylate therapy. On the 5th day of hospitalization, the electrocardiogram revealed a normal sinus rhythm with a 1st degree atrioventricular block. After discharge, the electrocardiogram normalized with the monthly penicillin injections. Herein we report a case of complete atrioventricular block associated with rheumatic fever. The heart block resolved without specific cardiac treatment, other than a non-steroidal anti-inflammatory medication

Clinical outcome of acute myocarditis in children according to treatment modalities

PurposeThere is currently little evidence to support intravenous immune globulin (IVIG) therapy for pediatric myocarditis. The purpose of our retrospective study was to assess the effects of IVIG therapy in patients with presumed myocarditis on survival and recovery of ventricular function and to determine the factors associated with its poor outcome.MethodsWe reviewed all consecutive cases of patients with myocarditis with left ventricular dysfunction verified by echocardiogram who had visited 3 university hospitals between January 2000 and September 2009. These patients were divided into 2 groups. Group 1 consisted of 23 patients (69.6%) who received IVIG alone or IVIG in combination with steroids, and group 2 consisted of 10 patients (30.3%) who received neither IVIG nor other immunosuppressive agents. Clinical manifestations, laboratory results, echocardiographic findings, and outcomes were compared between these 2 groups.ResultsOne year after the initial presentation, the difference in the probability of survival did not show statistical significance in IVIG-treated patients (P=0.607). Of the echocardiographic parameters on admission, a shortening fraction of less than 15% was associated with unremitting cardiac failure. Furthermore, anemic patients were more likely to have elevated N-terminal fragment levels of the B-type natriuretic peptide (NT-proBNP) in the progressed group (P=0.036).ConclusionThere was no difference between the IVIG-treated patients and the control patients in the degree of recovery of left ventricular function and survival. Prospective, randomized, clinical studies are needed to elucidate the effects of IVIG treatment during the acute stage of myocarditis on ultimate outcomes

Effect of Process Temperature on Density and Electrical Characteristics of Hf0.5Zr0.5O2 Thin Films Prepared by Plasma-Enhanced Atomic Layer Deposition

HfxZr1−xO2 (HZO) thin films have excellent potential for application in various devices, including ferroelectric transistors and semiconductor memories. However, such applications are hindered by the low remanent polarization (Pr) and fatigue endurance of these films. To overcome these limitations, in this study, HZO thin films were fabricated via plasma-enhanced atomic layer deposition (PEALD), and the effects of the deposition and post-annealing temperatures on the density, crystallinity, and electrical properties of the thin films were analyzed. The thin films obtained via PEALD were characterized using cross-sectional transmission electron microscopy images and energy-dispersive spectroscopy analysis. An HZO thin film deposited at 180 °C exhibited the highest o-phase proportion as well as the highest density. By contrast, mixed secondary phases were observed in a thin film deposited at 280 °C. Furthermore, a post-annealing temperature of 600 °C yielded the highest thin film density, and the highest 2Pr value and fatigue endurance were obtained for the film deposited at 180 °C and post-annealed at 600 °C. In addition, we developed three different methods to further enhance the density of the films. Consequently, an enhanced maximum density and exceptional fatigue endurance of 2.5 × 107 cycles were obtained

Plant Growth-Promoting Microorganism Pseudarthrobacter sp. NIBRBAC000502770 Enhances the Growth and Flavonoid Content of Geum aleppicum

Plant growth-promoting rhizobacteria are known to enhance the growth and antioxidant activity of several plants. However, the effects of such rhizobacteria on Geum aleppicum, a plant with pharmacological potential in Korea are unknown. In this study, we investigated the effects of Pseudarthrobacter sp. NIBRBAC000502770 treatment (100 mL/pot, every two weeks for 55 days), in the form of culture medium, 100−fold diluted culture, culture supernatant, and pelleted cells resuspended in water, on the growth, antibacterial activity and flavonoid content of G. aleppicum. The NIBRBAC000502770 strain showed high indole-3-acetic acid (IAA) content of 461.81 μg∙mL−1. The dry weight of the roots was significantly higher in the supernatant, diluted culture, and pellet-treated plants compared to that in the control plants. Additionally, the plant height, root length, leaf length, leaf width, chlorophyll content, biomass, and dry weight of the shoot were highest in the pellet-treated plants. Further, methanol extracts of pellet-treated plants showed significantly high flavonoid content compared to that in the control plants (28 mg∙g−1 vs. 7.5 mg∙g−1) and exhibited strong antibacterial activity against Gram-positive and negative bacteria. These results demonstrate the beneficial effects of Pseudarthrobacter sp. NIBRBAC000502770 on the growth and flavonoid content of G. aleppicum

Increased RANKL-mediated osteoclastogenesis by interleukin-1 beta and endoplasmic reticulum stress

Objective: The mechanism by which IL-1 beta and thapsigargin (TG)-induced endoplasmic reticulum (ER) stress modulate the receptor activator of nuclear factor kappa-B ligand (RANKL)-mediated osteoclastogenesis remains elusive. Thus, we investigated the osteoclast-specific and ER signals in osteoclastogenesis of bone marrow-derived cells. Methods: Bone marrow cells (BMCs) were obtained from 5-week-old male ICR mice and cultured to be differentiated into osteoclasts with M-CSF and RANKL in the presence or absence of IL-1 beta, TG, or 4-phenylbutyric acid (PBA), an ER stress-reducing drug. The formation of osteoclasts was evaluated by tartrate-resistant acid phosphatase (TRAP) staining and resorption pit assay with a dentine slice. The molecular mechanism of IL-1 beta and ER stress in osteoclastogenesis was investigated in BMCs transfected with siRNA for GRP78, PERK and IRE1 using reverse transcription-polymerase chain reaction and immunoblotting for osteoclast-specific and ER stress signaling molecules. Results: IL-1 beta and ER stress induced by TG-augmented the formation of osteoclasts, which was significantly inhibited by PBA and was mediated with osteoclast-specific signals, including c-Fos, NFATc1, and ER stress-associated signaling pathways, such as PERK, IRE1, GRP78, and eIF2 alpha. siRNA-mediated knockdown of ER stress signals inhibited the expression of NFATc1 and c-Fos, thus reducing IL-1 beta and/or TG-induced formation of osteoclasts. Conclusions: Osteoclastogenesis by IL-1 beta and/or ER stress is mainly associated with upregulation of eIF2 alpha, GRP78, PERK and IRE1. These results suggest that the signaling pathway of ER stress-induced osteoclast formation might be a new therapeutic target to prevent inflammatory and destructive arthritic disease such as RA and diverse osteoporosis. (C) 2014 Societe francaise de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.N

Immediate Effect of Serratus Posterior Inferior Muscle Direction Taping on Thoracolumbar Junction Rotation Angle During One Arm Lifting in the Quadruped Position

Background: The serratus posterior inferior (SPI) muscle originates from the spinous process of T11-L2 and inserts at the lower border of the 9–12th ribs. This muscle is involved in thoracolumbar rotation and stability. Several positions can be used to improve trunk stability; the quadruped position is a good position for easily maintaining a neutral spine. In particular, during one arm lifting, various muscles act to maintain a neutral trunk position, and the SPI is one of these muscles. If trunk stability is weakened, uncontrolled trunk rotation may occur at this time. Tape can be used to increase trunk stability. There have been no studies on the effect of taping applied to the SPI muscle on thoracolumbar junction (TLJ) stability. Objects: This study compared the TLJ rotation angle between three different conditions (without taping, transverse taping, and SPI muscle direction taping). Methods: Thirty subjects were recruited to the study (18 males and 12 females). The TLJ rotation angle was measured during one arm lifting in a quadruped position (ALQP). Two taping methods (transverse and SPI muscle direction taping) were applied, and the TLJ rotation angle was measured in the same movement. Results: SPI muscle direction taping significantly reduced TLJ rotation compared to that without taping (p < 0.001) and with transverse taping (p < 0.001). There was a significant difference in the TLJ rotation angle between transverse taping and SPI muscle direction taping (p < 0.017). Conclusion: SPI muscle direction taping reduces the TLJ rotation angle during ALQP. Therefore, SPI muscle direction taping is one method to improve TLJ stability and reduce uncontrolled TLJ rotation during ALQP