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Serum anti-Mullerian hormone (AMH) is a predictor of the pregnancy outcome in assisted reproductive technology (ART) cycles, particularly for older women. This study attempts to elucidate the effect of serum AMH on follicular hormone profiles and implantation outcome of the ensuing embryos in ART cycles. A total of 412 patients undergoing ART cycles at a private infertility center were included and 780 follicular fluid samples were collected. Levels of follicular hormones, including FSH, LH, inhibin B, AMH, estradiol, progesterone, and androstenedione were measured. The implantation outcome of the ensuing embryos was traced as a main outcome measure. We demonstrated that the follicular levels of estradiol, progesterone, and androstenedione were considerably similar, but the overall implantation rates increased as the serum AMH increased. Logistic regression analysis revealed that the best predictor for embryo implantation was follicular FSH (>9.64mIU/mL, odds ratio [OR] 0.9). Furthermore, serum AMH (Spearman's rho=-0.352) and female age (rho=0.369) are correlated with follicular FSH levels in those follicles. In conclusion, the serum AMH might affect follicular hormone profiles by interaction with gonadotrophin rather than with steroidogenesis. The follicular FSH levels are correlated with the implantation potential of the ensuing embryos., (Copyright © 2017. Published by Elsevier B.V.)

Background: Community-acquired pneumonia (CAP) is characterized as an acute inflammation of the lung associated with the activation of macrophages and neutrophils. Intercellular adhesion molecule-1 (ICAM-1) is an essential adhesion molecule involved in immune cell recruitment in lung inflammation. We investigated whether ICAM-1 is a useful biomarker for assessing the disease severity of hospitalized adult patients with CAP., Methods: Plasma soluble ICAM-1 (sICAM-1) levels were measured in 78 patients with CAP and 69 healthy controls by using a commercial enzyme-linked immunosorbent assay. The pneumonia severity index scores were used to determine CAP severity in patients upon initial hospitalization., Results: The sICAM-1 and C-reactive protein (CRP) levels decreased significantly in patients with CAP after antibiotic treatment. The plasma concentration of sICAM-1 alone, but not CRP, was correlated with CAP severity according to the pneumonia severity index scores (r=0.431, p<0.001). The sICAM-1 levels in patients with CAP with high mortality risk were significantly higher than those in patients with CAP with medium or low mortality risk. Moreover, the sICAM-1 level showed a significant correlation with the length of hospital stay (r=0.488, p<0.001). Mechanistic investigations found that bacterial lipopolysaccharide induced upregulation of ICAM-1 expression through the c-Jun N-terminal kinase pathway in RAW264.7 macrophages., Conclusions: Plasma sICAM-1 levels may play a role in the diagnosis and clinical assessment of CAP severity., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: We evaluated the ability of matrix metalloproteinase (MMP)-2, MMP-9, myeloperoxidase, osteopontin and stromal cell-derived factor 1 to predict mortality in hemodialysis (HD) patients., Methods: One hundred forty HD patients were enrolled and followed from December 2007 until December 2012. At the end of this 5-year period, data were compared between the patients who were alive and those who had died., Results: The patients who alive were younger (56 vs. 63y), with lower frequency of diabetes mellitus (34.34% vs. 58.53%), higher concentrations of albumin (4.13 vs. 3.91mg/dl) and lower concentrations of MMP-2 (430.76 vs. 521.59ng/ml). Multivariate analysis showed that age (HR=1.03, p=0.02), diabetes mellitus (HR=2.395, p=0.012), albumin (HR=0.475, p=0.047) and MMP-2 (HR=1.003, p=0.005) were independent factors predicting mortality in HD patients. Receiver operating characteristic curve analysis showed that albumin (AUC=0.628, p=0.027) and MMP-2 (AUC=0.643, p=0.004) had a similar ability (p=0.76) to predict survival of HD patients., Conclusions: Compared with albumin, serum MMP-2 is a non-inferior prognostic marker for predicting the survival of HD patients., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: The role of soluble CD40 ligand (sCD40L) in pelvic inflammatory disease (PID) remains unclear. We sought to determine whether sCD40L was an efficient serum marker as with WBC and CRP in PID patients., Methods: Enzyme-linked immunosorbent assay was used to measure the plasma levels of sCD40L before and after routine protocol treatments in sixty-four PID patients and seventy healthy controls., Results: The level of plasma sCD40L (pg/ml) was significantly elevated in PID patients (1632.83±270.91) compared to that in normal controls (700.33±58.77; p=0.001) and decreased significantly as compared to that in the same patients (928.77±177.25; p=0.0001) after they received treatment. The concentration of sCD40L was significantly correlated with the level of plasma C-reactive protein (CRP) in the blood (r=0.202, p=0.01, n=134). When the cutoff level of plasma sCD40L levels was determined to be 1612.26pg/ml based on ROC, the sensitivity, specificity, and the area under the curve of plasma sCD40L level for predicting PID were 0.26, 0.97, and 0.58 (95% confidence interval: 0.48-0.68), respectively, while the adjusted odds ratio (AOR) with their 95% CI of plasma sCD40L for PID risk was 7.09 (95% CI=1.14-43.87, p=0.03)., Conclusions: The expression of plasma sCD40L was increased in patients with PID and detection of plasma sCD40L could be useful for the diagnosis of PID., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Pneumonia is a worldwide infectious disease that is associated with significant morbidity and mortality and is the most common fatal infection acquired in hospitals. Despite advances in preventive strategies, such as antibiotic therapies and intensive care, the mortality rate still requires substantial improvement. Matrix metalloproteinases (MMPs) are a large family of zinc-dependent endopeptidases, which are known as the major enzymes responsible for the proteolytic degradation of proteinaceous components of the extracellular matrix (ECM). Although the main function of MMPs is the removal of the ECM during tissue resorption and progression of various diseases, MMPs also interact with multiple cytokines, participating in the pathology of infection and inflammation. This review presents a schematic overview of the different MMPs expressed in pneumonia. MMPs are key factors in the pathogenesis of various types of pneumonia, such as community-acquired pneumonia, hospital-acquired pneumonia, and ventilator-associated pneumonia. Here, we review the pathological roles of various MMPs in pneumonia., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Pelvic inflammatory disease (PID) is a common infection in women of reproductive age. However, diagnosis of PID can be difficult due to the wide variation in the symptoms and signs, ranging from subtle or mild symptoms to severe pain in the lower abdomen. Clinical diagnosis alone has only 87% sensitivity and 50% specificity. Therefore, identifying biological factors that are useful for early diagnosis and correlating their expression with the severity of PID could provide significant benefits to women suffering from PID. Pentraxin 3 (PTX3), E-cadherin, myeloperoxidase, stromal cell-derived factor 1 (SDF-1) and the matrix metalloproteinase-9 (MMP-9)/MMP-2 ratio are potential candidates for detecting PID reliably. As PID is often subtle, highly sensitive PID detection methods are needed to promote the prevention of severe sequelae. Growth arrest-specific 6 (Gas6), in combination with its soluble tyrosine kinase receptor, sAxl, could elevate the sensitivity to 92%, which was higher than all other markers tested. Moreover, PTX3, D-dimer and YKL-40 concentrations can predict the clinical course of PID. Although single nucleotide polymorphisms of biomarker genes are not associated with the development of PID, myeloperoxidase SNP -463 G/A and SDF-1 SNP 801 G/A may affect the aggravated expression of their biomarkers in PID., (Copyright © 2014. Published by Elsevier B.V.)

Background: We retrospectively investigated the relationship between immunohistochemical staining of radical prostatectomy (RP) specimens for snail and cancer recurrence., Methods: Seventy-six patients with prostate cancer who underwent RP were enrolled, and 53 patients were ultimately collected whose cancer was pathologically defined as T2. We detected the expression of snail using tissue microarrays. The snail image score was determined by the intensity×tumor percentage, and a high score was defined as 8 (1-12 points)., Results: The snail image scores and Gleason score sums were correlated with recurrence-free survival according to a log-rank test (p<0.05). In a Cox proportional hazard model, only a high snail image score (≥8) (hazard ratio (HR): 3.04, p=0.036) but not a high Gleason score sum (≥7) (HR: 1.33, p=0.215), and a more-advanced pathological T stage (T2c) (HR: 1.5, p=0.461) were significantly correlated with worse recurrence-free survival. The snail image score was determined to be an independent factor for predicting prostate cancer recurrence after RP., Conclusion: In patients with pathological localized prostate cancer and a high snail image score in cancer tissue, adjuvant therapy might be suggested to prevent early biochemical failure., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Backgrounds: To investigate the concentrations of plasma growth arrest-specific protein 6 (Gas6) and its soluble tyrosine kinase receptor sAxl in women with pelvic inflammatory disease (PID) and their association with clinical outcomes of PID., Methods: Blood specimens were consecutively collected from the 64 patients with PID before and after treatment and 70 healthy women in university hospital. Concentrations of plasma Gas6 and sAxl were detected using enzyme-linked immunosorbent assay., Results: The concentration of plasma Gas6 and sAxl was significantly increased in the patients with PID compared to the healthy controls, and then reduced significantly after treatment. Gas6 was significantly correlated with sAxl. When we selected 7.5 and 15.2 ng/ml as the cutoff concentration of plasma Gas6 and sAxl to detect PID respectively, the sensitivities of Gas6 and sAxl were 76.6% and 75.0%. When Gas6 and sAxl were combined, the sensitivity rose to 92.2%. They were not related to the incidences of tuboovarian abscesses and surgery, which were, however, significantly associated with length of hospital stay., Conclusions: Novel application of Gas6 or sAxl in combination had a high sensitivity to detect PID and is important in order to prevent severe sequelae., (© 2013.)

Background: Here, we have examined the plasma levels of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1), the MMP-9/TIMP-1 molar ratio, the TIMP-1 single nucleotide polymorphisms (SNPs) 372C/T and the susceptibility to community-acquired pneumonia (CAP)., Methods: An enzyme-linked immunosorbent assay (ELISA) was used to measure plasma MMP-9 and TIMP-1 concentrations in 60 patients with CAP and 60 healthy individuals. A polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay was used to detect the TIMP-1 SNPs 372C/T., Results: The plasma MMP-9, TIMP-1 levels and the MMP-9/TIMP-1 molar ratio were significantly increased in patients with CAP compared to normal controls. The MMP-9/TIMP-1 molar ratio decreased significantly in patients with CAP after treatment. Furthermore, the plasma TIMP-1 concentration was positively correlated with the pneumonia severity index (PSI), the CURB score, the results of the acute physiology and chronic health evaluation II (APACHE II) and the length of the hospital stay. No significant difference was found in the genotype distribution of TIMP-1 372C/T between patients with CAP and normal controls., Conclusions: We hypothesize that MMP-9 levels and the MMP-9/TIMP-1 molar ratio play a role in the development of CAP and are related to the severity of CAP. Based on our data, we suggest that incorporating plasma MMP-9 levels and the MMP-9/TIMP-1 molar ratio into a clinical evaluation will aid in CAP diagnosis., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Pneumonia is one of the most common causes of death from infectious diseases worldwide, and the most common fatal infection acquired in hospitals. Despite advances in prevention strategies, such as antibiotic therapies and intensive care, significant improvement in the mortality rate is still lacking. This high mortality is largely due to the limitations in current clinical practices and laboratory tests, which delay the timing of adequate antibiotic therapy. In recent years, many indicators (biomarkers) are present in scenarios where infectious pathogens invade into the body. These biomarkers, as reflected in specific biological responses to infections, have been reported to demonstrate the ability to facilitate the diagnosis, risk stratification, and management of pneumonia. This review provides a schematic overview of these new potential biomarkers based on the categories of (1) microorganisms and their derivatives, (2) inflammation mediators, (3) inflammation response proteins, and (4) stress-sensing proteins. In addition, approaches to identifying new biomarkers are also briefly introduced. Although no current biomarker can solely achieve a definitive diagnosis, many of them can be complemented, rather than replaced outright, in routine clinical practices to improve decision-making processes regarding pneumonia., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Background: To determine expression levels of urokinase-type plasminogen activator (uPA), soluble urokinase-type plasminogen activator receptor (suPAR), plasminogen activator inhibitor-1 (PAI-1) in plasma and to identify gene polymorphisms specific to patients with pelvic inflammatory disease (PID) and healthy controls., Methods: Enzyme-linked immunosorbent assay and polymerase chain reaction-restriction fragment length polymorphism were used to measure plasma levels and polymorphisms in uPA, suPAR, and PAI-1 among seventy healthy controls and 64 PID patients before and after they received routine treatment protocols., Results: The levels of plasma uPA (ng/ml) and soluble suPAR (pg/ml) were significantly increased in PID patients (uPA: 0.57±0.03; suPAR: 1372.04±68.20) when compared to that in normal controls (uPA: 0.55±0.06, p=0.002; suPAR: 1192.46±51.98, p=0.04); moreover, suPAR decreased significantly after treatment when compared to levels noted in the same patients (1220.06±58.14; p=0.003) after they received treatment. The increased expression of suPAR was significantly correlated with WBC counts (r=0.382, p=0.002, n=64) in blood as well as the plasma levels of CRP (r=0.441, p<0.0001, n=64) and uPA (r=0.426, p<0.0001, n=64) of PID patients prior to receiving treatment., Conclusions: Increased plasma suPAR could be a biological marker for the diagnosis of PID and may reflect a new focus in targeted therapy for pelvic inflammatory disease., (Copyright © 2012. Published by Elsevier B.V.)

Background: We identified the relationship between plasma level changes of cathepsin B and cystatin C before and after antibiotic treatment in hospitalized adult patients with community-acquired pneumonia (CAP)., Methods: We collected blood specimens from 61 adult patients with CAP before and after antibiotic treatment and from 60 healthy controls and measured the plasma concentrations of cathepsin B and cystatin C expression using the enzyme-linked immunosorbent assay (ELISA). The APACHE II, CURB-65, and Pneumonia Severity Index (PSI) scores were determined to assess CAP severity in patients upon initial hospitalization., Results: The results showed a decline in the number of WBCs and neutrophils, with decreases in the concentrations of CRP, cathepsin B, cystatin C, and the cathepsin B/cystatin C ratio being observed after antibiotic treatment. The plasma concentration of cathepsin B correlated with severity of CAP with the PSI score (r=0.290, p=0.025) and the CURB-65 score (r=0.258, p=0.047), respectively. The plasma concentration of cystatin C correlated with the APACHE II score (r=0.523, p<0.001), severity of CAP in the PSI score (r=0.721, p<0.001) and the CURB-65 score (r=0.609, p<0.001), respectively., Conclusions: Cathepsin B and cystatin C may play a role in the diagnosis and clinical assessment of the severity of CAP, which could potentially guide the development of treatment strategies., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Backgrounds: To detect the expression of plasma neutrophil gelatinase associated lipocalin (NGAL) and its complex with matrix metalloproteinase-9 (MMP-9) in patients with pelvic inflammatory disease (PID)., Methods: Enzyme-linked immunosorbent assay was used to measure the levels of plasma NGAL and NGAL/MMP-9 complex., Results: The levels of plasma NGAL or NGAL/MMP-9 complex were increased in patients with PID compared with those in normal controls and decreased significantly after treatment. Pre-treatment plasma level of NGAL was significantly correlated with WBC and neutrophil counts. In patients with PID, plasma level of NGAL/MMP-9 complex was correlated with plasma level of NGAL or MMP-9 significantly. In predicting PID, the sensitivities of NGAL and NGAL/MMP-9 complex were 76.6% and 78.1%; the negative predictive values, 72.7% and 74.5%., Conclusions: Plasma NGAL and NGAL/MMP-9 complex may act as diagnostic adjuvant biomarkers for PID. In patients with PID, about 80% have plasma levels of NGAL or NGAL/MMP-9 complex level >10.04 ng/ml or 2.33 ng/ml, respectively., (Copyright © 2011. Published by Elsevier B.V.)

Objective: Interleukin 23 receptor (IL-23R) plays a role in the pathogenesis of multiple autoimmune processes. The relationship between allograft outcomes and the IL-23Rvariant genotypes has not been reported on previously. Therefore, we examined the relationship between this genetic polymorphism and kidney transplant outcomes., Methods: This is an observational cohort study and 422 renal transplant recipients (RTRs) were enrolled. Polymerase chain reaction-restriction fragment length polymorphism was used for the measurement of IL-23R genetic polymorphisms. We used a composite end-point incorporating serum creatinine (SCr) doubling, graft failure and death as the primary outcome. Secondary outcomes included biopsy-proven acute rejection (BPAR), biopsy-proven interstitial fibrosis/tubular atrophy (IF/TA) and individual primary outcome. The risks of developing primary and secondary outcomes were compared between the different IL-23R genotypes and alleles., Results: With a mean follow-up of 79.3±28.8 months, 26 patients in the IL-23R genotype AA group and 32 patients in the IL-23R genotype AC/CC group reached the primary outcome (p=0.061). RTRs who carried the IL-23R AC/CC genotype (aHR 1.78; 95% CI. 1.01-3.12; p=0.046) and C allele (aHR 1.48; 95% CI. 0.96-2.28; p=0.075) had a higher risk of developing primary outcome as compared to those with IL-23R AA genotype and A allele, respectively. Moreover, RTRs who carried the IL-23R AC/CC genotype and C allele had a higher risk of developing biopsy-proven IF/TA (p=0.012; p=0.012) and SCr doubling (p=0.024; p=0.042) as compared to those with IL-23R AA genotype and A allele, respectively. The risk of BPAR, graft failure and death between the IL-23R genotypes and alleles were comparable., Conclusion: IL-23R polymorphism may have a potential immuno-modulating role in long-term allograft outcome., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Objective: Plasminogen activator inhibitor 1 (PAI-1) is thought to play a role in the pathogenesis of obesity and insulin resistance. A connection between gestational diabetes mellitus and the functional -675 PAI-1 genotype has been reported. Therefore, we examined the role of the PAI-1 gene polymorphism in kidney transplant recipients., Methods: A total of 376 kidney transplant recipients were prospectively screened for posttransplant diabetes mellitus (PTDM). Eighty-one (21.5%) patients were diagnosed with PTDM and the other 295 patients were non-diabetic following kidney transplantation. DNA samples were isolated from the sera and analyzed for the functional -675 4G/5G promoter polymorphisms of the PAI-1 gene., Results: Kidney transplant recipients with PTDM were significantly associated with tacrolimus use (p=0.03), older age (p=0.036), and higher body mass index (p=0.001). The genotype distribution was significantly different between the patients with PTDM (genotype 4G/4G:4G/5G:5G/5G=33.3%:60.5%:6.2%) and those without PTDM (genotype 4G/4G:4G/5G:5G/5G=36.9%:44.1%:19.0%) (p=0.018). Patients with homozygosity for 5G had a significantly lower rate of PTDM (aOR, 0.286, p=0.022) and higher cumulative event-free probability of time to PTDM (log rank test, p=0.0058)., Conclusion: Homozygosity for the 5G allele of the PAI-1 gene constitutes a protecting factor for the development of PTDM. Our findings are similar to a previous study on gestational diabetes mellitus, and strongly support a possible genetic role of PAI-1 in the development of PTDM., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Background: To relate the expression of the matrix degrading proteinase cathepsin B and its endogenous inhibitor cystatin C in the synovial fluid (SF) to the clinical and laboratory variables of joint inflammation in gouty arthritis of the knee., Methods: Thirty-nine SF samples were obtained from inflamed knees of patients with acute gout. The levels of cathepsin B, cystatin C, urokinase-type plasminogen activator (uPA), soluble uPA receptor (suPAR) and PA inhibitor type-1 (PAI-1), activities of matrix metalloproteinase-2 (MMP-2) and MMP-9, and cell counts as well as local arthritis activity scores (LAS) were examined., Results: The increases of cathepsin B levels correlated with increased leukocyte and neutrophil counts, latent MMP-9 (pro-MMP-9) activities, uPA, suPAR and PAI-1 levels, and uPA/PAI-1 ratios. Increased cystatin C levels corresponded closely with increased LAS, leukocyte and neutrophil counts, pro-MMP-9 activities, uPA, suPAR and PAI-1 levels, and uPA/PAI-1 ratios. Moreover, there was a correlation between cathepsin B and cystatin C levels., Conclusions: These results show a high correlation between the cathepsin B/cystatin C system and markers of joint inflammation in acute gout of the knee, demonstrating the pathologic role of cathepsin B and cystatin C in inflammation., (2010 Elsevier B.V. All rights reserved.)

Background: The role of bcl-2 expression, bcl-2 inhibitor HA14-1, and matrix metalloproteinase (MMP)-2 is still unclear in nasopharyngeal carcinoma (NPC)., Methods: From 1996 to 2000, 145 patients with newly diagnosed NPC who were treated with high dose radiotherapy were enrolled. The relationship between bcl-2 expression, TNM stage, and disease-specific survival was analyzed. Furthermore, the NPC cell line HONE-1 was used to confirm the relationship between bcl-2 and cell metastasis., Results: Among the 145 patients, 47 (32.4%) of them were bcl-2 positive. The expression of bcl-2 was significantly correlated with neck lymph node metastasis (p=0.006), and patients with negative bcl-2 expression had better disease-free survival (p=0.007). A Cox regression model revealed that only bcl-2 expression (p=0.023) and stage IV (p=0.043) were statistically significant in the prognosis of NPC. In vitro analysis also showed that treatment with the bcl-2 inhibitor HA14-1 exerted an inhibitory effect on migration and expression of MMP-2 in HONE-1 cells., Conclusions: Bcl-2 expression represents an important and easily assayed prognostic factor, and it may play an important role in lymph node metastasis. Inhibition of the migration mediated by MMP-2 may be a key feature for the prevention of cancer metastasis., (Copyright 2009 Elsevier B.V. All rights reserved.)

Background: Tissue inhibitors of metalloproteinases (TIMPs) are a family of multifunctional proteins known to possess a broad range of biological activities involved in tumorgenesis and mRNA expression of TIMP family members has been shown to be upregulated in numerous cancers and correlates with clinical outcomes. We investigated the association of TIMP-1 and TIMP-2 gene polymorphism with risk of endometrial cancer., Methods: In the present case-control study, we enrolled a total of 118 endometrial cancer patients confirmed by histopathology and 229 unrelated healthy individuals. Polymorphism for TIMP-1 (&#95;372C>T) and TIMP-2 (&#95;418G>C and &#95;303C>T) genes was genotyped by PCR-RFLP., Results: Frequency of TIMP-1&#95;372C/C genotype and 372-C allele differed significantly between patients with endometrial cancer (38.1% and 56.4% respectively) and healthy individuals (22.7% and 44.1% respectively). Individuals with TIMP-1&#95;372 C/C genotype were at higher risk of endometrial cancer (OR=2.37; 95%CI: 1.33-4.22). Stratification analysis showed that individuals with TIMP-1&#95;372 C/C genotype were at increased risk for endometrioid (OR=2.46; 95% CI 1.34-4.53) and low stage (stages I-II) endometrial cancer (OR=3.24; 95% CI 1.22-4.13). However, no significant differences in TIMP-2&#95;418G>C and TIMP-2&#95;303C>T genotypes were observed between endometrial carcinoma cases and controls., Conclusion: Individuals with TIMP-1&#95;372C/C genotype were at significantly higher risk of endometrial cancer.

Background: To test the hypothesis that naproxen, meloxicam and methylprednisolone down-regulate the plasminogen activator (PA)/plasmin system and gelatinases [matrix metalloproteinase (MMP)-2 and MMP-9] expression during early development of osteoarthritis (OA)., Methods: Samples of human OA articular cartilage, meniscus and synovium were obtained at knee arthroscopy and cultured ex vivo with or without naproxen, meloxicam or methylprednisolone. MMP-2 and MMP-9 levels were evaluated by gelatin zymography and urokinase-type PA (u-PA) and PA inhibitor-1 (PAI-1) levels were measured by enzyme-linked immunosorbent assay (ELISA)., Results: Gelatin zymography revealed that naproxen, meloxicam and methylprednisolone could suppress MMP-2 secretion in all tissue cultures and MMP-9 production in meniscal and synovial cultures. ELISA showed that naproxen and meloxicam reduced u-PA secretion in chondral and synovial cultures at 48 h except in naproxen-treated chondral cultures. On PAI-1 secretion, naproxen and meloxicam had the suppressive effects in all cultures at 48 h but not in naproxen-treated meniscal cultures. Methylprednisolone also decreased u-PA secretion in chondral and synovial cultures and PAI-1 production in synovial cultures at 48 h., Conclusion: Naproxen, meloxicam and methylprednisolone can down-regulate the PA/plasmin system and gelatinases expression in the early osteoarthritic knee of humans, thereby possibly have a potential structure-modifying activity in a limited use.

Background: Published reports concerning the expression of GST in various anemias including aplastic, hemolytic, iron deficiency and thalassemia anemia has been insufficient. We improved the conventional GST assay by incorporating a chloroform treatment to remove the interference of hemoglobin and evaluated the altered expression of GSTs in various anemias in Taiwan., Methods: We incorporated a chloroform treatment to eliminate the interference of hemoglobin. Erythrocyte total GST and isoenzymes activities from 35 control subjects and 125 subjects of various anemias, including aplastic, hemolytic, iron deficiency and thalassemia anemias were measured spectrophotometrically., Results: Chloroform treatment did not significantly affect GST activities in erythrocytes of control subjects while the activities of erythrocyte total GST and alpha-GST were significantly increased in all anemic patients (P<0.001). The expression of mu-GST was significantly decreased, although at a less extent, in cases of aplastic, iron deficiency and thalassemia anemia (P<0.05), but pi-GST was not physiologically different in various types of anemia., Conclusion: The determination of changes in erythrocyte GST activity is a promising indicator of oxidative stress conditions that occur in various types of anemia. Measurement of GST activity might be useful for the evaluation of prophylactic treatment in trials of antioxidant strategies.

Background: Lipoteichoic acid (LTA) and lipopolysaccharide (LPS), the toxicants from bacteria, are potent inducers of inflammatory cytokines, such as tumor necrosis factor-alpha (TNF) and interleukin-1beta (IL-1). Although LTA is much less reported than that on LPS, LTA is regarded as the gram-positive equivalent to LPS in some aspects. We investigated the LTA-induced signal transduction and biological effects, as well as to compare the effect of LTA with that of LPS., Methods: Kinase assay, ELISA and RT-PCR were performed to delineate LTA and LPS signaling as well as to determine the secretion and RNA expression of TNF and IL-1., Results: Src, Lyn and MAPKs are involved in LTA and LPS signaling in murine macrophages. Additionally, blockades of PKC, PI3K and p38, respectively, caused significant inhibition of both LTA- and LPS-induced proIL-1/IL-1 and TNF expression. ERK inactivation moderately reduced LTA- and LPS-induced proIL-1/IL-1, but considerably reduced TNF expression. Inhibition of JNK engendered super-induction of IL-1 secretion, but diminished TNF secretion. Strikingly, both IL-1 and TNF protein induction were declined by overexpression of dominant negative form of JNK., Conclusions: The results clarify the similarity and difference between LTA- and LPS-mediated signal transduction and induction of inflammatory cytokines in macrophages.

Background: Glucosamine sulfate may have an ex vivo inhibitory effect on the plasminogen activator (PA)/plasmin system and gelatinases expression during the early development of osteoarthritis (OA)., Methods: We compared the levels of urokinase-type PA (u-PA), PA inhibitor-1 (PAI-1) and gelatinases (matrix metalloproteinase-2 and -9 [MMP-2 and -9]) in a series of chondral, meniscal, and synovial cultures of early OA after treatment with or without glucosamine sulfate., Results: Gelatin zymography revealed that glucosamine sulfate could suppress MMP-2 secretion in chondral, meniscal and synovial cultures and also decrease MMP-9 production in synovial and meniscal cultures. ELISA data also showed the suppressive effects of glucosamine sulfate on u-PA and PAI-1 production in synovial cultures at 48 h., Conclusions: Our data suggest that one of the therapeutic effects of glucosamine sulfate is to down-regulate the expressions of u-PA, PAI-1, MMP-2 and MMP-9 that underlie the destruction of articular cartilage in the early stage of OA, and therefore to delay the joint failure.

Background: The involvements of matrix metalloproteinase-2 (MMP-2) in the pathogenesis of breast cancers have been established. We determined the concentrations of MMP-2 in serum samples and tumor tissues of breast cancer patients., Methods: Gelatin zymography and ELISA were used to measure MMP-2 and MMP-9 concentrations in 90 breast cancer patients, including 60 tissue samples and 30 serum samples., Results: ProMMP-2, activated MMP-2, proMMP-9 and activated MMP-9 levels were significantly higher in tumor tissues than that of corresponding paired adjacent normal tissue of 60 breast cancer patients (p<0.01). Further linear regression analysis has showed that the tumor size positively correlated with MMP-2 level in tumor tissue samples (R=0.55, p<0.0001), as well as with that of in serum samples (R=0.398, p=0.032). In addition, further statistical analysis for clinic pathological parameters revealed that MMP-2 level was significantly increased in patients with metastasis (p<0.05). Furthermore, MMP-2 level was significantly different between tumor grades (p=0.006)., Conclusions: MMP-2 levels in serum and tumor tissue might reflect the severity of invasion of breast cancer and various MMP inhibitors might be selectively used as potential anti-metastasis agents according to tumor size.

Background: It has been proven that extracellular matrix turnover is involved in the pathogenesis of various renal fibrosis diseases. Matrix metalloproteinase-2 and -9 (MMP-2 and -9) are the extracellular matrix degrading enzymes that are believed to play important roles in renal diseases. However, the relationship of circulating levels of MMP-2, -9 and serum creatinine in the patients of chronic kidney disease (CKD) has not yet been investigated., Methods: Gelatin zymography and ELISA were employed to measure MMP-2 and MMP-9 activities in the plasma samples of 60 CKD patients and 40 control subjects., Results: Serum creatinine concentrations and MMP-2 activities were significantly higher (p<0.001) while MMP-9 activity and creatinine clearance (CCr) were significantly lower (p<0.05 and p<0.001, respectively) in CKD patients, as compared with those of control subjects. In addition, serum creatinine concentrations correlated with MMP-2 activity (R=0.288, p<0.05) and inversely correlated with that of MMP-9 (R=0.344, p<0.01)., Conclusions: This study demonstrated a correlation between MMP-2, -9 and serum creatinine in CKD patients to suggest that MMP-2 and MMP-9 might contribute in the pathogenesis of CKD.

Background: The involvements of matrix metalloproteinase-9 (MMP-9) and urokinase plasminogen activator (uPA) in the pathogenesis of various types of lung cancers have been established. The aim of the present study was to determine the concentrations of MMP-9 and uPA in the plasma of nonsmall cell lung cancer (NSCLC) patients., Methods: Gelatin zymography and ELISA were used to measure MMP-9 and uPA concentrations, respectively, in 90 NSCLC patients and 50 control subjects., Results: Compared with that of control subjects, MMP-9 and uPA levels were significantly higher in the plasma of NSCLC patients (P<0.001 and P<0.01, respectively). Further statistical analysis for clinic pathological parameters revealed that MMP-9 and uPA levels were significantly increased in patients with metastasis (P<0.01 and P<0.05, respectively). Furthermore, the MMP-9 level was significantly different between smokers and nonsmokers (P<0.05) while uPA levels varied between histological types (P<0.05)., Conclusions: Plasma MMP-9 and uPA might play an important role in the metastasis of NSCLC by involvement in the processes of invasion and metastasis.

Background: It has been shown that matrix metalloproteinase-9 (MMP-9) is involved in the pathogenesis of various pulmonary inflammatory diseases. We determined the MMP-9 concentration in the plasma of community-acquired pneumonia (CAP) patients before and after antibiotic treatment., Methods: Gelatin zymography and ELISA analysis were used to measure MMP-9 activity and MMP-9 level, respectively, in 35 control subjects and 46 CAP patients., Results: WBC counts, neutrophils, MMP-9 activity and MMP-9 level were significantly higher in CAP patients compared with that of control subjects (P<0.001), while MMP-9 activity and MMP-9 level were returned to normal after the antibiotic treatment (P<0.001). In addition, MMP-9 level correlated positively with WBC counts and neutrophils number both before and after the antibiotic treatment., Conclusions: MMP-9 may play an important role in the pathogenesis of CAP with a positive correlation with the number of neutrophils.

Background: The aim of the present study was to determine the concentrations of cytosolic carbonic anhydrase (CA) isoenzymes in erythrocytes of patients with aplastic, autoimmune hemolytic, iron deficiency or beta-thalassemia anemia., Methods: Western blotting and CA esterase activity analysis were used to analyze cytosolic erythrocyte CA isoenzymes in 118 subjects with various types of anemia and 35 healthy controls., Results: Total CA activity and CAII concentration of anemia patients were significantly higher than that of the control subjects while CAI concentration was significantly lower in patients of autoimmune hemolytic anemia (P<0.01). Compared with controls, CAIII concentration was lower in iron deficiency anemia (P<0.01), but higher in beta-thalassemia anemia (P<0.001)., Conclusions: Carbonic anhydrase isoenzymes may contribute differently to various types of anemia. CAI may be an indicator to differentiate autoimmune hemolytic anemia from other types of anemia. CAII provides the CA activity necessary for maintaining ion transport in erythrocytes while CAIII may play an agent against oxidative damage in iron deficiency and beta-thalassemia anemia.

Background: Indicators for long-term monitor of the progress of hepatic diseases are of great clinical importance. Since elevated cathepsin was observed in liver diseases, the aim of this study is to investigate the involvement of cystatin C, a very potent inhibitor of cathepsin and a recently introduced marker for renal function, and to see the applicability of serum cystatin C being a convenient marker for the progression of liver diseases., Methods: One hundred eighty consecutive patients with chronic liver disease of various severities and 45 healthy controls were recruited to determine their serum cystatin C concentrations by N Latex Cystatin C kit, as well as certain relevant clinical values, including alanine transaminase (ALT), aspartate transaminase (AST) and AFP., Results: Average serum cystatin C concentration of patients with hepatic diseases was significantly higher than that of control (0.0902+/-0.0025 mg/dl vs. 0.067+/-0.007 mg/dl; p<0.001), and a linear regression analysis has revealed a direct relation between cystatin C and the severity of liver diseases (Y=1.172+5.492X, R(2)=0.088, p<0.001)., Conclusion: This study suggested that cystatin C may be an applicable monitoring marker for monitoring liver functions and progression of liver fibrosis.

Background: Clinically, gouty arthritis is associated with severe inflammation, such as pain, swelling and erythema of the joints. Gelatinase A and B (matrix metalloproteinase-2 and -9, MMP-2 and -9) participate in the degradation of the extracellular matrix (ECM) components in a variety of arthritis, especially in the inflammatory arthritis., Methods: We examined the levels of MMP-2 and -9 in 40 synovial fluids (SFs) from the knee joints of 24 patients with gouty arthritis and compared them with the clinical and laboratory variables of inflammation., Results: Gelatin zymography revealed that not only activated MMP-2 levels but also proMMP-9 levels in SF from the knee joints of gouty arthritis were associated with the local arthritis activity scores (LAS) (p < 0.001) and correlated well with the neutrophil counts in SF as well (p < 0.001). A similar correlation between proMMP-9 levels and LAS was also found within the individual patients before and during treatment with nonsteroidal antiinflammatory drugs (NSAIDs; p < 0.001). ProMMP-2 appeared in all SFs irrespective of LAS and neutrophil counts., Conclusions: The analysis of MMP-9 in SF samples can reveal the inflammatory condition of the knee joints with gouty arthritis. Joint aspiration may decrease the amount of MMPs in SF to attack the ECM of joint whether it is normal or not.

Background: This study was designed to evaluate the quantitative and activity alterations of cytosolic carbonic anhydrase (CA) isoenzymes in the erythrocytes of glucose-6-phosphate dehydrogenase (G6PD)-deficient individuals., Methods: Western Blot and CA esterase activity analysis were employed to measure cytosolic erythrocyte CA isoenzymes., Results: The total CA activities were analyzed from erythrocytes of 30 healthy and 30 G6PD-deficient individuals. The mean values with standard error (SE) were 22.9+/-1.69 U/gHb and 27.2+/-2.1 U/gHb (P<0.01), respectively. The ratio of CAI/CAII of G6PD-deficient individuals (1.28+/-0.06) was significantly lower than that of the normal subjects (3.79+/-0.18) (P<0.001). Furthermore, the concentration of CAIII in G6PD-deficient individuals was significantly lower than that of the normal subjects (P<0.001) and there were significant correlations between the concentration of CAI, CAII, CAIII, and ratio of CAI/CAII, and the activity concentration of G6PD., Conclusions: Different carbonic anhydrase isoenzymes may serve different roles in the G6PD-deficient erythrocyte. CAI could be used as an indicator for hemolytic anemia. CAII is able to compensate for the functions of CAI and increased expression of CAII will promote oxidative damage. CAIII can provide the G6PD-deficient persons with some extent of protection against oxidative damage.