Ultra-Fast Vitrification: Minimizing the Toxicity of Cryoprotective Agents and Osmotic Stress in Mouse Oocyte Cryopreservation.

Globally, women have been adopting oocyte cryopreservation (OC) for fertility preservation for various reasons, such as inevitable gonadotoxic treatment for specific pathologic states and social preferences. While conventional vitrification (C-VIT) has improved the success rate of OC, challenges of possible toxicities of high-concentration cryoprotective agents and osmotic stress persist. To overcome these challenges, we evaluated the ultra-fast vitrification (UF-VIT) method, which reduces the equilibration solution stage exposure time compared to C-VIT by observing mouse oocyte intracellular organelles and embryonic development. Consequently, compared to fresh mouse oocytes, UF-VIT presented significant differences only in endoplasmic reticulum (ER) intensity and mitochondrial (MT) distribution. Meanwhile, C-VIT showed substantial differences in the survival rate, key ER and MT parameters, and embryonic development rate. UF-VIT exhibited considerably fewer negative effects on key MT parameters and resulted in a notably higher blastocyst formation rate than C-VIT. Meiotic spindle (spindle and chromosomes) morphology showed no significant changes between the groups during vitrification/warming (VW), suggesting that VW did not negatively affect the meiotic spindle of the oocytes. In conclusion, UF-VIT seems more effective in OC owing to efficient cytoplasmic water molecule extraction, osmotic stress reduction, and minimization of cell contraction and expansion amplitude, thus compensating for the drawbacks of C-VIT.

Synergistic therapeutic combination with a CAF inhibitor enhances CAR-NK-mediated cytotoxicity via reduction of CAF-released IL-6.

BACKGROUND: Cancer-associated fibroblasts (CAFs) in the tumor microenvironment (TME) contribute to an impaired functionality of natural killer (NK) cells that have emerged as a promising therapeutic modality. The interaction between CAFs and NK cells within the TME exerts major inhibitory effects on immune responses, indicating CAF-targeted therapies as potential targets for effective NK-mediated cancer killing. METHODS: To overcome CAF-induced NK dysfunction, we selected an antifibrotic drug, nintedanib, for synergistic therapeutic combination. To evaluate synergistic therapeutic efficacy, we established an in vitro 3D Capan2/patient-derived CAF spheroid model or in vivo mixed Capan2/CAF tumor xenograft model. The molecular mechanism of NK-mediated synergistic therapeutic combination with nintedanib was revealed through in vitro experiments. In vivo therapeutic combination efficacy was subsequently evaluated. Additionally, the expression score of target proteins was measured in patient-derived tumor sections by the immunohistochemical method. RESULTS: Nintedanib blocked the platelet-derived growth factor receptor ß (PDGFRß) signaling pathway and diminished the activation and growth of CAFs, markedly reducing CAF-secreted IL-6. Moreover, coadministration of nintedanib improved the mesothelin (MSLN) targeting chimeric antigen receptor-NK-mediated tumor killing abilities in CAF/tumor spheroids or a xenograft model. The synergistic combination resulted in intense NK infiltration in vivo. Nintedanib alone exerted no effects, whereas blockade of IL-6 trans-signaling ameliorated the function of NK cells. The combination of the expression of MSLN and the PDGFRß+-CAF population area, a potential prognostic/therapeutic marker, was associated with inferior clinical outcomes. CONCLUSION: Our strategy against PDGFRß+-CAF-containing pancreatic cancer allows improvements in the therapy of pancreatic ductal adenocarcinoma.

A Lignan from Alnus japonica Activates Myogenesis and Alleviates Dexamethasone-induced Myotube Atrophy.

To find inhibitors against skeletal muscle loss, we isolated a lignan compound ((-)-(2R,3R-1,4-O-diferuloylsecoisolarciresinol, DFS) from the stem of Alnus japonica. C2C12 myoblasts were treated with DFS during differentiation. To induce an in vitro atrophic condition, differentiated myotubes were treated with dexamethasone (a synthetic glucocorticoid). DFS (10 nM) increased expression levels of myogenic factors and the number of multi-nucleated myotubes expressing myosin heavy chain (MHC). The myogenic potential of DFS could be attributed to p38 MAPK activation. DFS also protected against dexamethasone-induced damage, showing increased expression of MHC and mammalian target of rapamycin (mTOR), a major anabolic factor. Under atrophic condition, the anti-myopathy effect of DFS was associated with inactivation of NF-κB signaling pathway and the subsequent suppression of muscle degradative E3 ligases and myostatin. DFS treatment also restored fast muscle fiber (type II a, II b, and II x), known to be susceptible to dexamethasone. These results indicate that DFS isolated from A. japonica can stimulate myogenesis via p38 MAPK activation and alleviate muscle atrophy by modulating the expression of genes associated with muscle protein anabolism/catabolism. Thus, we propose that DFS can be used as a pharmacological and nutraceutical agent for increasing muscle strength or protecting muscle loss.

A lignan from Alnus japonica inhibits glioblastoma tumorspheres by suppression of FOXM1.

Forkhead Box M1 (FOXM1) is known to regulate cell proliferation, apoptosis and tumorigenesis. The lignan, (-)-(2R,3R)-1,4-O-diferuloylsecoisolariciresinol (DFS), from Alnus japonica has shown anti-cancer effects against colon cancer cells by suppressing FOXM1. The present study hypothesized that DFS can have anti-cancer effects against glioblastoma (GBM) tumorspheres (TSs). Immunoprecipitation and luciferase reporter assays were performed to evaluate the ability of DFS to suppress nuclear translocation of ß-catenin through ß-catenin/FOXM1 binding. DFS-pretreated GBM TSs were evaluated to assess the ability of DFS to inhibit GBM TSs and their transcriptional profiles. The in vivo efficacy was examined in orthotopic xenograft models of GBM. Expression of FOXM1 was higher in GBM than in normal tissues. DFS-induced FOXM1 protein degradation blocked ß-catenin translocation into the nucleus and consequently suppressed downstream target genes of FOXM1 pathways. DFS inhibited cell viability and ATP levels, while increasing apoptosis, and it reduced tumorsphere formation and the invasiveness of GBM TSs. And DFS reduced the activities of transcription factors related to tumorigenesis, stemness, and invasiveness. DFS significantly inhibited tumor growth and prolonged the survival rate of mice in orthotopic xenograft models of GBM. It suggests that DFS inhibits the proliferation of GBM TSs by suppressing FOXM1. DFS may be a potential therapeutic agent to treat GBM.

Kazinol C from Broussonetia kazinoki stimulates autophagy via endoplasmic reticulum stress-mediated signaling.

Autophagy modulators are considered putative therapeutic targets because of the role of autophagy in cancer progression. Kazinol C, a 1,3-diphenylpropane from the plant Broussonetia kazinoki, has been shown to induce apoptosis in colon cancer cells through the activation of AMPK at high concentrations. In the present study, we found that Kazinol C induced autophagy through endoplasmic reticulum stress-mediated unfolded protein response signaling in several normal and cancer cell lines at low concentrations of Kazinol C that did not induce apoptosis. Kazinol C activated the transducers of unfolded protein response signaling, leading to target gene expression, LC3-II conversion, and TFEB nuclear translocation. Chemical inhibition of endoplasmic reticulum stress reduced LC3-II conversion. In addition, blockade of autophagy by knockout of Atg5 or treatment with 3-MA enhanced Kazinol C-induced apoptosis. In summary, we have uncovered Kazinol C as a novel autophagy inducer and confirmed the role of autophagy as a cellular stress protector.

Urushiol V Suppresses Cell Proliferation and Enhances Antitumor Activity of 5-FU in Human Colon Cancer Cells by Downregulating FoxM1.

Colorectal cancer (CRC) is one of the most common malignant tumor. 5-FU is commonly used for the treatment of CRC. However, the development of drug resistance in tumor chemotherapy can seriously reduce therapeutic efficacy of 5-FU. Recent data show that FoxM1 is associated with 5-FU resistance in CRC. FoxM1 plays a critical role in the carcinogenesis and drug resistance of several malignancies. It has been reported that urushiol V isolated from the cortex of Rhus verniciflua Stokes is cytotoxic to several types of cancer cells. However, the underlying molecular mechanisms for its antitumor activity and its potential to attenuate the chemotherapeutic resistance in CRC cells remain unknown. Here, we found that urushiol V could inhibit the cell proliferation and induced S-phase arrest of SW480 colon cancer cells. It inhibited protein expression level of FoxM1 through activation of AMPK. We also investigated the combined effect of urushiol V and 5-FU. The combination treatment reduced FoxM1 expression and consequently reduced cell growth and colony formation in 5-FU resistant colon cancer cells (SW480/5-FUR). Taken together, these result suggest that urushiol V from Rhus verniciflua Stokes can suppress cell proliferation by inhibiting FoxM1 and enhance the antitumor capacity of 5-FU. Therefore, urushiol V may be a potential bioactive compound for CRC therapy.

Synthesis of improved long-chain isomaltooligosaccharide, using a novel glucosyltransferase derived from Thermoanaerobacter thermocopriae, with maltodextrin.

Isomaltooligosaccharide (IMO), considered to be a prebiotic, reportedly has health effects, particularly in terms of digestion; however, the prebiotic effects of IMOs depend largely on the degree of polymerization. Currently, IMOs are commercially produced using transglucosidase (TG) derived from Aspergillus niger. Here, we report a novel Thermoanaerobacter thermocopriae-derived TG (TtTG) that can produce long-chain IMOs (L-IMOs) using maltodextrin as the main substrate. A putative carbohydrate-binding gene comprising carbohydrate-binding module 35 and glycoside hydrolase family 15 domain was cloned and successfully overexpressed in Escherichia coli BL21 (DE3) cells. The resulting purified recombinant enzyme (TtTG) had a molecular mass of 94 kDa. TtTG displayed an optimal pH of 4.0 (higher than that of commercial TG) and an optimal temperature of 60 °C (same as that of commercial TG). TtTG also enabled the synthesis of oligosaccharides using various saccharides, such as palatinose, kojibiose, sophorose, maltose, cellobiose, isomaltose, gentiobiose, and trehalose, which acted as specific acceptors. TtTG could also produce a medium-sized L-IMO, different from that by dextran-dextrinase and TG, from maltodextrin, as the sole substrate. Thus, the novel combination of maltodextrin and TtTG shows potential as an effective method for commercially producing L-IMOs with improved prebiotic effects.

Neutrophil extracellular trap clearance by synovial macrophages in gout.

BACKGROUND: Monosodium urate (MSU) crystals, i.e., the central etiological factors in gouty arthritis, induce the formation of neutrophil extracellular traps (NETs). We investigated whether synovial macrophages could clear NETs as a self-resolution mechanism in acute gouty arthritis. METHODS: Synovial fluid mononuclear cells (SFMCs) were incubated with NETs induced by MSU crystals. NET engulfment was determined based on neutrophil elastase (NE), myeloperoxidase (MPO), and SYTOX Green signals within synovial fluid CD14+ cells. In addition, the correlations between CD14+ cells, MPO-dsDNA complexes, and expression of pro- and anti-inflammatory cytokines were analyzed in the synovial fluid CD14+ macrophages of patients with gouty arthritis. RESULTS: Synovial fluid CD14+ macrophages significantly engulfed the MSU crystal-induced NETs, as evidenced by the alteration in SYTOX Green intensity or the presence of NE and MPO in the cytoplasm of CD14+ cells. The proportion of CD14+ macrophages was significantly and inversely correlated with levels of MPO-dsDNA complex in the synovial fluid of gout patients. Synovial fluid CD14+ macrophages cultured with NETs did not show a significant induction in pro- and anti-inflammatory cytokines. CONCLUSION: Synovial fluid macrophages may play an important role in the resolution of MSU crystal-induced gouty inflammation by clearing NETs without causing any significant immunological response.

Considering serum alanine aminotransferase and gamma-glutamyltransferase levels together strengthen the prediction of impaired fasting glucose risk: a cross-sectional and longitudinal study.

Emerging data suggest that an increase in serum alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) as biomarkers of oxidative stress are associated with increased risk of impaired fasting glucose (IFG). The present study was an investigation of whether an increase in serum ALT and GGT had a combined effect on increasing IFG risk through cross-sectional and longitudinal studies. In the cross-sectional study, data were analyzed from 9937 subjects without diabetes who underwent health check-ups between 1999 and 2001 (baseline data). In the longitudinal study, 6390 subjects were analyzed who had been rechecked between 2009 and 2014, excluding IFG patients from baseline data. In cross-sectional analysis, adjusted odds ratio (OR) of IFG in the fourth quartile of both ALT and GGT was 1.829 (95% confidence interval [CI] 1.545-2.164) compared with the reference group (1st and 2nd quartiles of ALT and GGT). In longitudinal analysis, IFG probability increased gradually with an increase in the circulating levels of ALT and GGT. Adjusted hazard ratios for developing IFG in the fourth quartile of both ALT and GGT was 1.625 (95% CI 1.263-2.091) compared with the reference group (1st and 2nd quartiles). Increased serum ALT and GGT levels are well associated with IFG after potential confounders are adjusted for, and elevated ALT and GGT at the same time can have a combined effect in predicting the development of IFG.

Discovery of 5-Phenoxy-2-aminopyridine Derivatives as Potent and Selective Irreversible Inhibitors of Bruton's Tyrosine Kinase.

As a member of the tyrosine protein kinase Tec (TEC) family, Bruton's tyrosine kinase (BTK) is considered a promising therapeutic target due to its crucial roles in the B cell receptor (BCR) signaling pathway. Although many types of BTK inhibitors have been reported, there is an unmet need to achieve selective BTK inhibitors to reduce side effects. To obtain BTK selectivity and efficacy, we designed a novel series of type II BTK inhibitors which can occupy the allosteric pocket induced by the DFG-out conformation and introduced an electrophilic warhead for targeting Cys481. In this article, we have described the structure-activity relationships (SARs) leading to a novel series of potent and selective piperazine and tetrahydroisoquinoline linked 5-phenoxy-2-aminopyridine irreversible inhibitors of BTK. Compound 18g showed good potency and selectivity, and its biological activity was evaluated in hematological tumor cell lines. The in vivo efficacy of 18g was also tested in a Raji xenograft mouse model, and it significantly reduced tumor size, with 46.8% inhibition compared with vehicle. Therefore, we have presented the novel, potent, and selective irreversible inhibitor 18g as a type II BTK inhibitor.

Anti-Melanogenesis Activity of 6-O-Isobutyrylbritannilactone from Inula britannica on B16F10 Melanocytes and In Vivo Zebrafish Models.

A potential natural melanogenesis inhibitor was discovered in the form of a sesquiterpene isolated from the flowers of Inula britannica, specifically 6-O-isobutyrylbritannilactone (IBL). We evaluated the antimelanogenesis effects of IBL on B16F10 melanocytes and zebrafish embryos. As a result, we found that 3-isobutyl-1-methylxanthine (IBMX)-induced melanin production was reduced in a dose-dependent manner in B16F10 cells by IBL. We also analyzed B16F10 cells that were and were not treated with IBMX, investigating the melanin concentration, tyrosinase activity, mRNA levels. We also studied the protein expressions of microphthalmia-associated transcription factor (MITF), tyrosinase, and tyrosinase-related proteins (TRP1, and TRP2). Furthermore, we found that melanin synthesis and tyrosinase expression were also inhibited by IBL through the modulation of the following signaling pathways: ERK, phosphoinositide 3-kinase (PI3K)/AKT, and CREB. In addition, we studied antimelanogenic activity using zebrafish embryos and found that the embryos had significantly reduced pigmentation in the IBL-treated specimens compared to the untreated controls.

Lignan from Alnus japonica Inhibits Adipocyte Differentiation via Cell Cycle and FOXO1 Regulation.

In the present study, we isolated a lignan ((-)-(2R,3R)-1,4-O-diferuloylsecoisolariciresinol, DFS) from Alnus japonica and evaluated its antiobesity potential in vitro. We also determined its mechanism of action in a mouse pre-adipocyte 3T3-L1 cell line. DFS dose- and day-dependently inhibited adipogenesis by downregulation of adipogenic factors and lipid metabolism-regulating factors during adipocyte differentiation. In particular, DFS suppressed cell cycle-regulating factors and induced G0/G1 cell cycle arrest, implying that it had an inhibitory effect on mitotic clonal expansion which occurred at an early stage of adipogenesis. DFS also suppressed adipogenesis through decreasing Akt phosphorylation and increasing the level of Forkhead box protein-O1 (FOXO1). These results suggest that DFS may be a pharmacological candidate for the development of antiobesity, therapeutic, and nutraceutical products.

The Antimelanogenic Effect of Inularin Isolated from Flowers of Inula britannica on B16F10 Melanoma Cells and Zebrafish Embryos.

In the search for novel, natural melanogenesis inhibitors, a new sesquiterpene, inularin, was isolated from the flowers of Inula britannica, and the structure was determined using spectroscopic and chemical methods. The antimelanogenic effects of inularin on B16F10 melanoma cells and zebrafish embryos were evaluated. Inularin dose-dependently reduced melanocyte-stimulating hormone-induced melanin production and L-DOPA oxidation in B16F10 cells. Zebrafish embryos were used to confirm the antimelanogenic activity. Inularin significantly decreased the pigmentation of embryos compared with untreated controls.

Broussoflavonol B from Broussonetia kazinoki Siebold Exerts Anti-Pancreatic Cancer Activity through Downregulating FoxM1.

Pancreatic cancer has a high mortality rate due to poor rates of early diagnosis. One tumor suppressor gene in particular, p53, is frequently mutated in pancreatic cancer, and mutations in p53 can inactivate normal wild type p53 activity and increase expression of transcription factor forkhead box M1 (FoxM1). Overexpression of FoxM1 accelerates cellular proliferation and cancer progression. Therefore, inhibition of FoxM1 represents a therapeutic strategy for treating pancreatic cancer. Broussoflavonol B (BF-B), isolated from the stem bark of Broussonetia kazinoki Siebold has previously been shown to inhibit the growth of breast cancer cells. This study aimed to investigate whether BF-B exhibits anti-pancreatic cancer activity and if so, identify the underlying mechanism. BF-B reduced cell proliferation, induced cell cycle arrest, and inhibited cell migration and invasion of human pancreatic cancer PANC-1 cells (p53 mutated). Interestingly, BF-B down-regulated FoxM1 expression at both the mRNA and protein level. It also suppressed the expression of FoxM1 downstream target genes, such as cyclin D1, cyclin B1, and survivin. Cell cycle analysis showed that BF-B induced the arrest of G0/G1 phase. BF-B reduced the phosphorylation of extracellular signal-regulated kinase ½ (ERK½) and expression of ERK½ downstream effector c-Myc, which regulates cell proliferation. Furthermore, BF-B inhibited cell migration and invasion, which are downstream functional properties of FoxM1. These results suggested that BF-B could repress pancreatic cancer cell proliferation by inactivation of the ERK/c-Myc/FoxM1 signaling pathway. Broussoflavonol B from Broussonetia kazinoki Siebold may represent a novel chemo-therapeutic agent for pancreatic cancer.

Inhibition of autophagy sensitizes lignan-induced endoplasmic reticulum stress-mediated cell death.

Relationship between autophagy and endoplasmic reticulum (ER) stress and their application to treat cancer have been actively studied these days. Recently, a lignan [(-)-(2R, 3R)-1,4-O-diferuloylsecoisolariciresinol, DFS] from Alnus japonica has been found to reduce the viability of colon cancer cells. In this study, we have observed DFS-induced autophagy in a variety of cancer cell lines. In addition, DFS led to ER stress, based on the activation of unfolded protein response (UPR) transducers and an elevated expression of UPR target genes in prostate and colon cancer cells. Further investigation has shown that DFS triggered the activation of AMP-activated protein kinase (AMPK) signaling and nuclear translocation of transcription factor EB (TFEB). Furthermore, the cytotoxicity of DFS was potentiated by the co-treatment of autophagy inhibitor in these cancer cells. This study has provided a noble implication that the combination of DFS and autophagy inhibition exerts a synergistic effect in cancer treatment.

Immunological characteristics and possible pathogenic role of urinary CD11c+ macrophages in lupus nephritis.

OBJECTIVES: Kidney-infiltrating immune cells can contribute to the pathogenesis of lupus nephritis (LN). We investigated the immunological characteristics of CD11c+ macrophages and their functions associated with the pathogenesis of LN. METHODS: CD11c+ macrophages were examined in the urine samples of patients with LN. Phenotypic markers and pro-inflammatory cytokine expression levels were analysed by flow cytometry. To determine the origin of urinary macrophages, peripheral monocytes were treated with sera from patients with systemic lupus erythematosus (SLE). The pathogenic role of CD11c+ macrophages in tubulointerstitial damage was investigated using SLE sera-treated monocytes and HK-2 cells. RESULTS: Urinary CD11c+ macrophages expressed pro-inflammatory cytokines, such as IL-6 and IL-1ß, and resembled infiltrated monocytes rather than tissue-resident macrophages with respect to surface marker expression. CD11c+ macrophages had high expression levels of the chemokine receptor CXCR3, which were correlated with cognate chemokine IP-10 expression in urinary tubular epithelial cells. When treated with sera from SLE patients, peripheral monocytes acquired the morphological and functional characteristics of urinary CD11c+ macrophages, which was blocked by DNase treatment. Finally, SLE sera-treated monocytes induced fibronectin expression, apoptosis and cell detachment in HK-2 cells via production of IL-6. CONCLUSION: CD11c+ macrophages may be involved in the pathogenesis of tubulointerstitial injury in LN.

Z-Ajoene Inhibits Growth of Colon Cancer by Promotion of CK1α Dependent ß-Catenin Phosphorylation.

Aberrant activation of a Wnt/ß-catenin pathway results in nuclear accumulation of ß-catenin in colon cancer. Inhibiting ß-catenin is one strategy for treating colon cancer. Here, we identified Z-ajoene, a sulfur containing compound isolated from crushed garlic, as an inhibitor of colon cancer cell growth. Z-Ajoene repressed ß-catenin response transcriptional activity, intracellular ß-catenin levels, and its representative target protein levels (c-Myc and cyclin D1) in SW480 colon cancer cells. To clarify the regulatory mechanism of decreased ß-catenin levels, we examined the effect of Z-ajoene on ß-catenin phosphorylation, which is involved in ß-catenin degradation. Z-Ajoene promoted the phosphorylation of ß-catenin at Ser45 in a casein kinase 1α (CK1α)-dependent manner, which is an essential step in ß-catenin degradation in the cytosol. These findings indicate that Z-ajoene from garlic may be a potential chemotherapeutic agent by modulating CK1α activity and the Wnt/ß-catenin signaling pathway.

Effect of digital scans on marginal and internal discrepancies of zirconia crowns.

STATEMENT OF PROBLEM: A few studies have compared the accuracy of newly introduced intraoral scanners (IOSs); however, limited evidence is available concerning which system provides the best marginal and internal adaptation of zirconia crowns. PURPOSE: The purpose of this in vitro study was to compare the marginal and internal discrepancies of zirconia crowns fabricated with 4 digital scanners by a silicone replica technique. MATERIAL AND METHODS: A maxillary central incisor was prepared for a ceramic crown and duplicated to form 10 metal abutments. Four groups of zirconia crowns with different scanning methods were produced for each die: 1 laboratory scanner, L (Ceramill Map 400), and 3 different IOSs, CS (CS3600), TR (TRIOS3), and CE (CEREC Omnicam). The marginal and internal discrepancies were measured by a silicone replica technique under a static load of 50 N. The replica specimens were sectioned buccolingually and mesiodistally and then examined by using a stereomicroscope (JTZ-7XT) at ×200 magnification. Fifteen reference points were measured on each specimen. One-way ANOVAs with the Duncan multiple range tests were used for statistical analysis of the data (α=.05). RESULTS: The mean marginal discrepancies of zirconia crowns were 12.7 µm for group L, 12.6 µm for group CS, 14.8 µm for group TR, and 15.8 µm for group CE. No significant differences were found in marginal and incisal discrepancies among 4 groups. However, groups CS and L showed significantly better cervical and axial discrepancies than groups TR and CE. Group TR showed significantly better axial discrepancy than group CE. CONCLUSIONS: Zirconia crowns made by using the CS3600 and the laboratory scanner with a conventional impression showed significantly better internal discrepancies than those made by using TRIOS3 and CEREC Omnicam.

Prominent Inflammatory Features of Monocytes/Macrophages in Acute Calcium Pyrophosphate Crystal Arthritis: a Comparison with Acute Gouty Arthritis.

Calcium pyrophosphate (CPP) crystals can present as acute inflammatory arthritis which is known as an acute CPP crystal arthritis. Although monocytes/macrophages have been shown to play a role in the initiation of crystal-mediated inflammatory responses, differences in their phenotypes between acute CPP crystal arthritis and acute gouty arthritis have not yet been investigated. We examined the immunological characteristics of synovial monocytes/macrophages in patients with acute CPP crystal and acute gouty arthritis. CD14+CD3-CD19-CD56- cell frequencies in synovial fluid mononuclear cells (SFMCs) were measured. Expression of pro- and anti-inflammatory cytokines and markers was determined. The SFMCs were dominated by a population of monocytes/macrophages in acute CPP crystal arthritis similar to that in acute gout. Synovial monocytes/macrophages showed the phenotypes of infiltrated monocytes as shown by expression of CD88, C-C chemokine receptor type 2, myeloid-related protein (MRP)8 and MRP14 but not proto-oncogene tyrosine-protein kinase MER. Comparatively, the CD14+ cells from patients with acute CPP crystal arthritis had similar high levels of IL-1ß and TNF-α production but significantly lower expression of IL-10 and M2 marker (CD163). The monocytes/macrophages had the capacity to produce IL-8 in response to CPP crystals. Proinflammatory features were more dominant in monocytes/macrophages during acute CPP crystal arthritis than those during acute gouty arthritis.