Quercetin-induced pyroptosis in colon cancer through NEK7-mediated NLRP3 inflammasome-GSDMD signaling pathway activation.

Pyroptosis, a gasdermin-mediated lytic cell death, is a new hotspot topic in cancer research, and induction of tumor pyroptosis has emerged as a new target in cancer management. Quercetin (Que), a natural substance, demonstrates promising anticancer action. However, further information is required to fully comprehend the function and mechanism of Que in pyroptosis in colon cancer. This study revealed the underlying mechanism of Que-induced pyroptosis in colon cancer in vitro and in vivo. Que inhibited colon cancer cell growth through gasdermin D (GSDMD)-mediated pyroptosis. Depletion of GSDMD, rather than gasdermin E (GSDME), reversed the cytotoxic effects of Que on colon cancer cells. Que treatment upregulated NIMA-related kinase 7 (NEK7) protein expression, thus facilitating the assembly of the NLRP3 inflammasome and cleavage of GSDMD. NEK7 silencing resulted in colon cancer cell growth in vitro and in vivo. Mechanistically, NEK7 depression restrained the activation of the NLRP3 inflammasome-GSDMD pathway, thus attenuating pyroptosis triggered by Que in colon cancer cells. Furthermore, lower NEK7 and NLRP3 expression levels indicated colon cancer progression. Our results unveiled a novel pattern of anti-colon cancer activity of Que, and activation of NEK7-mediated pyroptosis is potentially a promising therapeutic target for colon cancer, which provides novel experimental proof for the clinical application of Que.

Progressive algorithm for the scattering of electromagnetic waves by a multilayered eccentric sphere.

This paper presents a general progressive algorithm for the computational study of electromagnetic wave scattering by a multilayered eccentric nanoparticle. The presented methodology is based on a combination of the vector addition theorem for spherical wave functions and an efficient progressive algorithm that matches the boundary conditions of every two adjacent shell layers from the outmost to the innermost layer. As a result, only a solution of small-sized matrices is required rather than solving a large set of system equations as reported in other works. With the developed approach, explicit expressions of the Mie scattering coefficients of the eccentric particle can be obtained. Moreover, the Mie coefficients of a specific inner layer could be calculated selectively, instead of having to compute those of all layers of the entire particle as required by other algorithms. The presented methodology can be used to study practically any type of spherical particle inclusions and the most widely studied cases such as scattering by solid particles, concentric particles, and inclusions with centers displaced along a straight line are just special cases of the algorithm presented. Computed results are also presented, illustrating that the eccentric structure allows extra freedom in the design of multilayered nanoparticles for optical applications.

Efficient progressive algorithm for light scattering of a multilayered concentric nanoparticle.

An efficient progressive methodology is presented for the computation of multi-scattering of electromagnetic waves by a multilayered concentric nanoparticle. Instead of solving a large set of system equations as reported in other works, the proposed approach utilizes a progressive algorithm which considers two adjacent shell layers at a time, marching progressively from the innermost to the outmost layer, and requires only multiplication of 4×4 matrices. The progressive algorithm yields the analytical expression for the scattering parameter of the concentric particle. Moreover, the progressive algorithm allows the scattering coefficients of a specific internal layer to be computed selectively, rather than having to calculate those of all layers of the entire particle as required by other algorithms. We show that the presented progressive method has equivalent accuracy to the well-known recursive algorithm, but it is more attractive due to its lower complexity in implementation. It is shown that light scattering of both a single solid sphere and two-layered concentric shell are special cases of the proposed methodology. Case study demonstrates that the presented methodology is useful in assisting the design of a multilayered core/shell structure with maximum forward scattering feature, indicating it is applicable to the exploration of optical phenomena of nanoparticles with numerous layers. Moreover, the present progressive algorithm is further extended to the electromagnetic scattering by an eccentric multilayered particle with inner cores displaced along a line defined by the centers of the spheres, which provides extra freedoms for the design of optical core shell spherical particles.

Fabrication of Hierarchical Micro/Nano Compound Eyes.

Fabrication of a hierarchical macro-/micro-/nano compound eye is presented in this paper. This bioinspired compound (BIC) eye is obtained by an integrated manufacturing technology that combines (i) nanoimprinting, (ii) picosecond laser swelling, and (iii) air-assisted deformation. The diameter and height of nanopillars, microlens, and macrobase can be controlled precisely by fine-tuning the process parameters. The multifunctional properties of the BIC eye, such as superhydrophobicity, antireflection, and other optical characteristics, are investigated. It is found that the microlens with nanopillars can effectively improve the surface wettability with a contact angle of 152° and contact angle hysteresis of 12°, and enhance transmittance by 2% over the wavelength range of 200-1200 nm. Moreover, the final hierarchical compound eye exhibits the excellent imaging properties and a wide field-of-view of 120° without distortion. These multifunctional properties will enable the widespread application of the compound eye in diverse real-time environmental conditions.

Nanoscale 3D temperature gradient measurement based on fluorescence spectral characteristics of the CdTe quantum dot probe.

The existing quantum dot temperature measurement techniques can only measure the planar temperature in the cell but fails in 3D temperature investigation. We present a novel method of measuring the 3D temperature field on nano scale, combining fluorescence spectral characteristics of the CdTe quantum dot probe with optical spatial positioning. Based on dual-helix point spread function, a 3D temperature optical measurement system with a resolution of 0.625 °C is established, providing a new perspective of 3D temperature measurement inside the cell. We thus offer an original research tool for further revealing the evolution process of secretions in cell metabolism.

Quantum 3D thermal imaging at the micro-nanoscale.

Real-time and accurate measurement of three-dimensional (3D) temperature field gradient maps of cells and tissues would provide an effective experimental method for analyzing the coupled correlation between metabolism and heat, as well as exploring the thermodynamic properties of nanoparticles under complex environments. In this work, a new principle of quantum 3D thermal imaging is proposed. The photoluminescence principle of quantum dots is expounded and CdTe QDs are prepared by aqueous phase synthesis. Fluorescence spectral characteristics of QDs at different temperatures are studied. The optimized algorithm of the optical spot double helix point spread function is proposed to improve the imaging, where optimized light energy increased by 27.36%. The design scheme of a quantum 3D thermal imaging system is presented. The measurement range is (-8 mm, +8 mm). The temperature is calculated according to the temperature-heat curve of quantum dots. The double helix point spread function has converted the defocus distance of QDs into the rotation angle of the double optical spot, thereby determining its position. The experimental results reveal that real-time 3D tracking and temperature measurements of quantum dots at the micro-nanoscale are achieved. Overall, the proposed nano-scale 3D quantum thermal imaging system with high-resolution may provide a new research direction and exploration of many frontier fields.

Liquid chromatography-mass spectrometry-based quantitative proteomics analysis reveals chondroprotective effects of astragaloside IV in interleukin-1ß-induced SW1353 chondrocyte-like cells.

OBJECTIVE: Chondrocyte apoptosis played a key role on the progression of Osteoarthritis (OA). Safe and effective drugs are urgently needed for the treatment of OA. Previous study reported that Astragaloside IV (ASG-IV) had exerted a protective effect against articular cartilage degeneration by promoting rapid proliferation of chondrocyte. Therefore, the aim of our study is to explore the effects and mechanisms of ASG-IV in chondrocyte apoptosis. METHODS: Isobaric Tags For Relative And Absolute Quantitation (iTRAQ)-based quantitative proteomics was used to quantitatively detect and map proteins in SW1353 chondrocyte-like cells pre-treated with ASG-IV or interleukin-1ß (IL-1ß) or ASG-IV+IL-1ß. The iTRAQ-labeled peptides were fractionated by high-accuracy liquid chromatography-mass spectrometry (LC-MS). Cell apoptosis and differentially expressed proteins was detected by flow cytometry (FCM), quantitative real-time polymerase chain reaction (qRT-PCR), and western blotting, respectively. RESULTS: The apoptosis of the IL-1ß-induced SW1353 cells treated with ASG-IV was greatly inhibited. Bioinformatics analysis revealed that gamma actin 1 (ACTG1) and Yes Associated Protein 1 (YAP1), participating in the Hippo signaling pathway and Vitronectin (VTN) and Collagen Type I Alpha 1 Chain (COL1A1), involving in the extracellular matrix (ECM)-receptor interaction signaling pathway, were all significantly up-regulated in the IL-1ß-induced SW1353 cells after treatment with ASG-IV. The qRT-PCR and Western blotting results confirmed the up-regulation of these four genes. CONCLUSION: ASG-IV played a positive role in human osteoarthritic chondrocyte apoptosis, possibly through modulation of the Hippo signaling pathway by up-regulating YAP1and ACTG1 expression, and also by up-regulating VTN and COL1A1, which are involved in the ECM-receptor interaction pathway. Taken together, all the results suggested that ASG-IV had a novel therapeutic potential for the treatment of OA.

Icariin inhibits MMP­1, MMP­3 and MMP­13 expression through MAPK pathways in IL­1ß­stimulated SW1353 chondrosarcoma cells.

Osteoarthritis (OA) is the most common type of arthritis and is a leading cause of disability worldwide, resulting in pain, reduced quality of life and socioeconomic burden. Current therapies for OA focus on mitigating the symptoms of advanced disease, but novel therapeutic agents are needed to inhibit the processes leading to OA. The present study aimed to investigate the effects of Icariin on matrix metalloproteinase (MMP)­1, MMP­3 and MMP­13 expression in interleukin (IL)­1ß­stimulated human SW1353 chondrosarcoma cells, and to investigate the possible mechanism underlying the chondroprotective effects of Icariin. In the present study, IL­1ß was applied on SW1353 chondrosarcoma cells to mimic the microenvironment of osteoarthritis. The cells were treated with Icariin and mitogen­activated protein kinase (MAPK) signaling pathway activators or inhibitors. MMP­1, MMP­3, MMP­13, phosphorylated (P)­p38, P­c­Jun N­terminal kinase (JNK) and P­extracellular signal­regulated kinase (ERK) expression was assessed using reverse transcription­quantitative polymerase chain reaction, ELISA and western blot analysis. The results of the present study demonstrated that Icariin inhibited the expression of MMP­1, MMP­3, MMP­13, P­p38, P­ERK and P­JNK. Furthermore, it was revealed that the inhibition of p38 and ERK contributed to the inhibition of MMP­1 and MMP­3 by Icariin, whereas the inhibition of p38 and JNK contributed to the inhibition of MMP­13. The present results suggested that Icariin may have a chondroprotective effect, exerted through the inhibition of MMP­1, MMP­3 and MMP­13 via MAPK pathways. Therefore, Icariin may have potential as a novel therapeutic strategy for the treatment of osteoarthritis.

Matrine regulates Th1/Th2 cytokine responses in rheumatoid arthritis by attenuating the NF-κB signaling.

To investigate the efficacy and mechanisms of matrine, a component derived from Sophora flavescens in treatment of rheumatoid arthritis (RA), a rat model of RA was established. Compared to control rats, matrine significantly mitigated inflammation and severity of RA (paw volume and articular index (AI) score). Using either mice splenic T cells stimulated with PMA/ionomycin or rat splenic T cells, the levels of Th1 and Th2 responses were determined by flow cytometry, quantitative RT-PCR, and ELISA. Furthermore, the levels of NF-κBp65 (RelA), IκBα, and phosphor-IκBα in T cells were determined by Western blot. Our study found that matrine modulated the imbalance of Th1 and Th2 cytokine responses in rats with RA by reducing the levels of Th1 cytokines (IFN-γ, TNF-α, IL-1ß), but increasing Th2 cytokine (IL-4 and IL-10) through attenuating the NF-κB signaling in T cells, suggesting matrine as a promising drug for intervention of RA.

Matrine induces the apoptosis of fibroblast-like synoviocytes derived from rats with collagen-induced arthritis by suppressing the activation of the JAK/STAT signaling pathway.

The induction of apoptosis-resistant rheumatoid synovial tissue cells has been related to constitutively active Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling in rheumatoid arthritis (RA). The excessive proliferation and inherent resistance to apoptosis of fibroblast-like synoviocytes (FLS) is an important mechanism by which RA originates. However, the effects of matrine on FLS in RA is unclear. The present study aimed to investigate the mechanism of action of matrine in a rat model of collagen­induced arthritis (CIA). The CIA model was established using bovine type II collagen. FLS were isolated from control and CIA rats, cultured in vitro, and confirmed to harbor fibroblast­like characteristics. After treatment of FLS with varying conc-entrations of matrine, the JAK2 inhibitor AG490, or a combination of both drugs, cell proliferation, apoptosis rate, expression of apoptotic markers and the activation of the JAK/STAT pathway were assessed. Additionally, CIA rats were administered either matrine or methotrexate by oral gavage to examine the effects of therapeutic intervention on arthritis pathogenesis. The arthritis index (AI) was measured and ankle joint structure was analyzed histologically to determine the severity of CIA. Furthermore, expression levels of apoptotic markers and members of the JAK/STAT family were also examined in vivo. Compared with the CIA group, matrine reduced AI and improved ankle pathology. Matrine also inhibited FLS proliferation, induced G0/G1 cell cycle arrest, and increased the rate of apoptosis in vitro. The effects of matrine on apoptosis induction were further confirmed by observations that Bcl-2 levels were decreased, whereas Bax and caspase-3 levels were increased in the matrine-treated synovial tissues and FLS. Finally, matrine treatment also diminished the phosphorylation, and hence activation of JAK2, STAT1 and STAT3. Our results suggest that matrine induces the apoptosis of FLS from rats with CIA by inhibiting activation of the JAK/STAT signaling pathway.

Clinical efficacy of 'Spleen-kidney-care' Yiqi Huayu and Jiangzhuo traditional Chinese medicine for the treatment of patients with diabetic nephropathy.

The aim of the present study was to investigate the effect of the traditional Chinese medicine (TCM), 'Spleen-kidney-care' Yiqi Huayu and Jiangzhuo decoction (SKC-YJ), as an adjuvant therapy in diabetic nephropathy (DN) treatment. In total, 72 patients with DN were randomly divided into control (n=54) and experimental (n=18) groups, with the latter administered SKC-YJ treatment. Indicators for determining the condition of the patients included the levels of proteinuria, blood glucose, glycosylated hemoglobin, blood lipids, blood viscosity and C-reactive protein, which were used to analyze the treatment protocols for DN. Following SKC-YJ treatment, the urinary albumin excretion rate, fasting blood glucose, 2 h-postprandial blood glucose, glycosylated hemoglobin, triglyceride, total cholesterol, blood viscosity, fibrinogen and C-reactive protein levels were detected in the two groups, and were all demonstrated to decrease significantly following treatment with SKC-YJ. Furthermore, the results revealed that SKC-YJ treatment exhibited no significant side-effects on the blood, liver and renal functions or gastrointestinal reactions. By contrast, SKC-YJ improved the symptoms of nausea, vomiting and diarrhea in the patients with DN, while showing no allergic reaction during the observation period. Therefore, SKC-YJ treatment was shown to significantly improve the clinical efficacy of DN treatment, illustrating novel roles for TCM in DN treatment.

Ginsenoside Rb1 inhibits matrix metalloproteinase 13 through down-regulating Notch signaling pathway in osteoarthritis.

Mounting evidence suggests that an excess of matrix metalloproteinase-13 (MMP-13) plays an important role in the breakdown of extracellular matrix in osteoarthritis (OA). Here, the effects of ginsenoside Rb1 (GRb1) on the expression of MMP-13 in IL-1ß-induced SW 1353 chondrosarcoma cells and an experimental rat model of OA induced by anterior cruciate ligament transection (ACLT) were investigated. SW1353 chondrosarcoma cells were pretreated with or without GRb1 and Notch signaling pathway inhibitor, DAPT, then were stimulated with IL-1ß. In rats, experimental OA was induced by ACLT. These rats then received intra-articular injections of vehicle, an inhibitor of γ-secretase, DAPT, and/or GRb1. Expression of MMP-13, collagen type II (CII), Notch1, and jagged 1 (JAG1) were verified by western blotting and immunohistochemistry. In addition, levels of MMP-13 mRNA were detected using quantitative real-time PCR. In histological analyses, treatment with DAPT reduced the number of cartilage lesions present and the expressions of MMP-13, CII, Notch1, and JAG1. In addition, treatment with GRb1 was associated with lower levels of Notch1 and JAG1 in both IL-1ß-induced SW1353 chondrosarcoma cells and in the rat OA model. Furthermore, the suppressive effect of GRb1 on MMP-13 was greater than that exhibited by the signaling pathway inhibitor. In conclusion, GRb1 inhibits MMP-13 through down-regulating Notch signaling pathway in OA.

Fuyuan Decoction Enhances SOX9 and COL2A1 Expression and Smad2/3 Phosphorylation in IL-1ß-Activated Chondrocytes.

Fuyuan Decoction (FYD), a herbal formula in China, has been widely used for osteoarthritis (OA) treatment. Herein, we determined the effects of FYD on the expression of transcription factor SOX9 and its target gene collagen type II, alpha 1 (COL2A1) as well as the activation of Smad2/3 in interleukin- (IL-) 1ß-stimulated SW1353 chondrosarcoma cells. Serum-derived FYD (FYD-CS) was prepared to treat SW1353 cells with or without SB431542, a TGF-ß1 receptor inhibitor. Cell cycle progression was tested by flow cytometry. The expression of SOX9 and COL2A1 and the activation of Smad2/3 (p-Smad2/3) were analyzed by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and/or western blot. The results showed that, after treatment, FYD-CS, while inducing S-phase cell cycle arrest, enhanced cell proliferation and protected the cells against IL-1ß- and/or SB431542-induced cell growth inhibition. Furthermore, FYD-CS reversed the decreased expression of COL2A1 and SOX9 induced by IL-1ß and SB431542 and blocked the decreased phosphorylation of Smad2/3 induced by IL-1ß alone or in combination with SB431542. Our results suggest that FYD promotes COL2A1 and SOX9 expression as well as Smad2/3 activation in IL-1ß-induced chondrocytes, thus benefiting cell survival.

Effects of icariin on the regulation of the OPG-RANKL-RANK system are mediated through the MAPK pathways in IL-1ß-stimulated human SW1353 chondrosarcoma cells.

Arthrodial cartilage degradation and subchondral bone remodeling comprise the most predominant pathological changes in osteoarthritis (OA). Moreover, accumulating evidence indicates that the abnormal expression of osteoprotegerin (OPG), receptor activator of nuclear factor kappa-B ligand (RANKL) and receptor activator of nuclear factor kappa-B (RANK) plays a vital role in the collapse of cartilage and subchondral bone. In the present study, the effects of icariin on the expression levels of these 3 factors in interleukin (IL)-1ß-stimulated SW1353 chondrosarcoma cells were investigated. The SW1353 chondrosarcoma cells were cultured in the presence or absence of icariin and mitogen-activated protein kinase signaling pathway inhibitors, and were then stimulated with IL-1ß. Cell viability was assessed by MTT assay. The mRNA and protein expression of OPG, RANKL and RANK was analyzed by quantitative reverse transcription polymerase chain reaction (RT-qPCR) and ELISA, respectively. In addition, the levels of phosphorylated p38 (p-p38) and phosphorylated extracellular signal-regulated kinase (p-ERK)1/2 were detected by western blot analysis. The results from western blot analysis revealed that treatment with icariin decreased the levels of p-p38 and increased the levels of p-ERK1/2 in the IL-1ß-stimulated SW1353 cells. In addition, treatment with icariin decreased the levels of RANK and RANKL. Furthermore, the suppressive effects of icariin on OPG and OPG/RANKL were greater than those exhibited by the p38 signaling pathway inhibitor (SB203580). The findings of the the present study suggest that icariin has therapeutic potential for use in the treatment of OA.

Knockdown of peroxiredoxin 5 inhibits the growth of osteoarthritic chondrocytes via upregulating Wnt/ß-catenin signaling.

Peroxiredoxin 5 is a member of the peroxiredoxin family, which has been shown to act as an antioxidant whose main function is to reduce reactive oxygen species in cells. Peroxiredoxin 5 has been found to be abnormally elevated in human osteoarthritic chondrocytes. However, the detailed mechanism by which peroxiredoxin 5 modulates human osteoarthritic chondrocytes' survival has not been elucidated. In the current study, we demonstrated that peroxiredoxin 5 knockdown activated osteoarthritic chondrocytes apoptosis, and decreased scavenging of endogenous reactive oxygen species. Furthermore, silencing of peroxiredoxin 5 resulted in an altered expression of proteins associated with Wnt signaling. Collectively, these results demonstrated that the regulatory effects of peroxiredoxin 5 can be partially attributed to Wnt/ß-catenin signaling.

Experimental chondrocyte hypertrophy is promoted by the activation of discoidin domain receptor 2.

The aim of the present study was to assess the association between chondrocytes and the extracellular matrix (ECM), and determine whether this contributes to osteoarthritis (OA). Chondrocyte hypertrophy was measured in articular cartilage samples from early-stage OA patients. In addition, rat chondrocytes were cultured and divided into four groups (A to D): Group A was an untreated control group, group B was incubated with chicken collagen II, group C was transfected with the discoidin domain of discoidin domain receptor-2 (DDR2) and group D was transfected with full­length DDR2. The expression levels of DDR2 and hypertrophic markers in each group were then measured by quantitative polymerase chain reaction (qPCR) and western blot analyses. Chondrocyte hypertrophy was identified in samples of early­stage OA patients. In rat chondrocyte cultures, the relative mRNA and protein expression levels of hypertrophic markers were determined as: Group D > B > C > A. In conclusion, transfection with DDR2 induced the expression of hypertrophic markers, as assessed by qPCR and western blot analyses. DDR2 therefore promoted chondrocyte hypertrophy and terminal differentiation.

Chondroprotective effects and multi-target mechanisms of Icariin in IL-1 beta-induced human SW 1353 chondrosarcoma cells and a rat osteoarthritis model.

Cartilage degradation is the most predominant pathological change during osteoarthritis (OA). Furthermore, accumulating evidence suggests that an excess of matrix metalloproteinase-13 (MMP-13) plays a critical role in the breakdown of cartilage. Here, the effects of Icariin on the expression of MMP-13 in IL-1ß-induced SW 1353 chondrosarcoma cells were investigated. In addition, the in vivo effects of Icariin on an experimental rat model of OA induced by anterior cruciate ligament transection (ACLT) was examined. SW1353 chondrosarcoma cells were pretreated with or without Icariin and MAPK and Wnt/ß-catenin signaling pathway inhibitors, then were stimulated with IL-1ß. In rats, experimental OA was induced by ACLT. These rats then received intra-articular injections of vehicle, signaling pathway inhibitors, and/or Icariin. Expression of MMP-13, phosphorylated p38, phosphorylated JNK, and ß-catenin were verified by western blotting. In addition, levels of MMP-13 mRNA were detected using quantitative real-time PCR. In histological analyses, treatment with Icariin reduced the number of cartilage lesions present. In addition, treatment with Icariin was associated with lower levels of phosphorylated p38, phosphorylated JNK, and ß-catenin in both IL-1ß-induced SW1353 chondrosarcoma cells and in the rat OA model. Furthermore, the suppressive effect of Icariin on MMP-13 was greater than that exhibited by other signaling pathway inhibitors. Overall, these data suggest that Icariin has therapeutic potential for the treatment of OA.

Effect of Chinese traditional herb Epimedium grandiflorum C. Morren and its extract Icariin on osteoarthritis via suppressing NF-kappaB pathway.

Osteoarthritis (OA), which is also called degenerative arthritis, is the leading cause of disabilities in the old people. The Chinese traditional herb Epimedium grandiflorum had long been found to attenuate osteoarthritis process, but the detailed mechanism was not clear. To study the mechanisms of E. grandiflorum in the treatment of osteoarthritis, rabbit osteoarthritis model combined with D-galactose was used. After different treatments for 10 weeks, cartilage sections were analyzed by immunohistochemistry for uPA, uPAR and PAI expression level. E. grandiflorum could significantly attenuate OA condition and decrease uPA, uPAR and PAI expression. The extract of E. grandiflorum, icariin also had a similar effect when compared with E. grandiflorum treatment alone. Rabbit chondrocytes were further isolated to be stimulated by TNFalpha combined with different reagents treatment. Here, icariin treatment significantly reduced nuclear factor kappa B NF-kappaB (P65) activity, decreased uPA expression level and increased Ikappabetaalpha protein level. The results indicated that E. grandiflorum and its extract icariin could attenuate OA condition, reduce the expression of uPA and uPAR and increase PAI in experimental rabbit model and this effect may be conducted by suppressing NF-kappaB activity by increasing IkappaBalpha level.

Fuyuan Decoction inhibits nitric oxide production via inactivation of nuclear factor-κB in SW1353 chondrosarcoma cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Fuyuan Decoction (FYD) is an empirical formula of treating Bi Zheng in traditional Chinese medicine (TCM). Despite the fact that the efficiency of FYD on treating osteoarthritis has been verified in clinic, the underlying mechanisms are not totally understood. This study was to investigate the effects and mechanisms of FYD on nitric oxide (NO) production and nuclear factor (NF)-κB activation in interleukin (IL)-1ß-stimulated chondrocytes. MATERIALS AND METHODS: SW1353 human chondrosarcoma cells were pretreated with various concentrations of FYD-containing serum (FYD-CS), and then were stimulated by IL-1ß. Amounts of NO were determined by Griess reaction assay. Inducible NO synthase (iNOS) expression, inhibitor-κBα (IκBα) degradation and nuclear translocation of p65 protein were determined by Western blot assay. DNA binding activity of NF-κB was determined by ELISA assay using Trans AM(™) kit for p65. RESULTS: 10% and 20% (v/v) FYD-CS significantly decreased NO production in a concentration-dependent manner (p<0.05 or p<0.01) as compared to control in IL-1ß-induced SW1353 cells. Besides, 10% and 20% FYD-CS also significantly reduced iNOS protein expression by about 60% and 70% (both p<0.01), respectively. Furthermore, 10% and 20% FYD-CS markedly decreased IκBα degradation by about 45% and 26% (p<0.01 or p<0.05), lessened P65 content in the nucleus by about 28% and 60% (both p<0.01), and repressed DNA binding activity of P65 by about 30% and 45% (both p<0.01) in IL-1ß-induced SW1353 cells. CONCLUSIONS: These findings suggested that FYD could inhibit NO production and iNOS expression in IL-1ß-induced chondrocytes through suppressing NF-κB activation.

Propylthiouracil-induced autoimmune syndromes: 11 case report.

The objective of this study was to report 11 cases of propylthiouracil (PTU)-induced autoimmune syndromes. We describe the clinical presentation, course, and outcome of 11 patients and compare clinical features between PTU-induced lupus and PTU-induced vasculitis. Of our 11 patients, 7 patients had vasculitis and 4 patients had lupus. Patients with vasculitis were older and had a longer duration of treatment in comparison with lupus. P-ANCA were predominantly found in PTU-induced vasculitis, but also found in lupus, while ANA and anti-dsDNA were often found in lupus. Some difference of renal and pulmonary involvement was often found between PTU-induced vasculitis and lupus. Most of patients needed steroids or immunosuppressive drugs. Vasculitis in the cases of PTU-induced autoimmune phenomena is often found than lupus. P-ANCA in both PTU-induced lupus and vasculitis can all present, but there are differences in clinical and outcome features to diagnosis.