Biomedical subjects

Xin Zhang

Publications and source records attributed to Xin Zhang.

At least 55 records · Page 3Linked to original sources

PubMed2006

Antiviral treatment of hepatitis B virus-transgenic mice by a marine organism, Styela plicata.

AIM: To evaluate the antiviral effect of the effective ingredient of Styela plicata in a murine model of hepatitis B virus carrier. METHODS: HBV-transgenic mice were divided into 3 groups (control group, lamivudine treatment group and the effective ingredient of Styela plicata treatment group) and assigned to receive normal diet, lamivudine or the effective ingredient of Styela plicata for consecutive weeks. Serum hepatitis B surface antigen was detected by enzyme-linked immunosorbent assay (ELISA) method. Serum HBV DNA was detected by real-time polymerase chain reaction (RT-PCR). Serum T helper (h) 1 cytokine interleukin (IL)-2 and Th2 cytokine IL-6 were detected by the quantitative sandwich enzyme immunoassay technique. Another group of HBV-transgenic mice was assigned to receive the effective ingredient of Styela plicata for consecutive weeks. The histology of liver tissue was evaluated before and after treatment. RESULTS: Twelve weeks after starting the therapy, serum hepatitis B surface antigen was significantly lowered in Styela plicata -treated mice and lamivudine-treated mice compared with the mice receiving normal diet (F(12wk) = 88.81, P(12wk) = 0.000<0.01). Serum HBV DNA was significantly lowered in Styela plicata -treated mice and lamivudine-treated mice compared with the mice receiving normal diet (F(12wk) = 20.71, P(12wk) = 0.000<0.01). However, like lamivudine, the effective ingredient of Styela plicata could not inhibit the replication of HBV completely. A rebound phenomenon of hepatitis B surface antigen and HBV DNA in sera could be found 4 wk after withdrawal of medication. Eight weeks after starting the therapy, serum levels before and after Styela plicata treatment of IL-2 were 2.41 +/- 0.38 and 10.56 +/- 0.78 ng/L, respectively (t(8wk) = -16.51, P(8wk) = 0.000<0.01). Compared with the serum levels of IL-2 in the normal diet-treated mice (2.48+/-0.17 ng/L; t(8wk) = 13.23, P(8wk) = 0.000<0.01). Serum levels before and after Styela plicata treatment of IL-6 were 63.62 +/- 6.31 and 54.52 +/- 6.22 ng/L, respectively, compared with the serum levels of IL-6 in the normal diet-treated mice (60.84 +/- 4.21 ng/L). Histological analysis of liver from Styela plicata-treated HBV-transgenic mice also showed catabatic status in inflammation and hepatitis B surface antigen. CONCLUSION: Styela plicata may be an effective antiviral medicine in treating chronic hepatitis B.

Animals↗

PubMed2006

Physicochemical properties of low molecular weight alkylated chitosans: a new class of potential nonviral vectors for gene delivery.

Low molecular weight chitosans grafted with N-/2(3)-(dodec-2-enyl)succinoyl groups (HM-LMW-chitosans) with a mean molecular mass of 5 kDa, a degree of acetylation of 3% and a degree of tetradecenoyl substitution (TDC) of 3-18 mol% have been synthesized. These molecules are monodisperse and soluble in water at neutral pH. Using tensiometry and Nile Red fluorescence, the HM-LMW-chitosans were found to form micelles through hydrophobic interactions involving their tetradecenoyl chains and nonprotonated glucosamine monomers. Their critical micelle concentration decreases with increasing TDC values but varies little with pH and salt. Interaction with large unilamellar vesicles taken as model membranes indicated that HM-LMW-chitosans interact mainly with vesicles mimicking the inner leaflet of biomembranes both through electrostatic and hydrophobic interactions. This preferential interaction may destabilize endosomal membranes and favor the DNA release into the cytoplasm in gene delivery applications. Moreover, since this interaction significantly decreased the membrane fluidity of these vesicles, the HM-LMC-chitosans are thought to exhibit limited lateral mobility and flip-flop ability, and thus, limited cytotoxicity. These properties suggest that the HM-LMW-chitosans may constitute a promising new class of nonviral vectors for gene therapy.

Alkylation↗

PubMed2006

Pax6 is regulated by Meis and Pbx homeoproteins during pancreatic development.

Pancreatic development depends on the transcription factor Pax6, which controls islet cell differentiation and hormone production. To understand the regulation of Pax6 pancreatic expression, we have identified a minimal Pax6 pancreatic enhancer and show that it contains a composite binding site for Meis and Pbx homeoproteins. We further show that Meis proteins are expressed during pancreatic development, and together with Pbx, are able to form a synergistic binding complex on the Pax6 pancreatic enhancer. When tested in transgenic mice, both the Meis and Pbx sites are essential for Pax6 pancreatic enhancer activity, and the composite site can be functionally replaced by a consensus Meis-Pbx sequence. In addition, analysis of Pbx1 and Pbx2 knockout mice demonstrates that, during pancreatic islet formation, Pax6 expression becomes dependent upon Pbx1 and Pbx2 function. As Meis homeoproteins have been previously demonstrated to regulate Pax6 expression during lens development, these results suggest a conserved mechanism of Pax6 regulation by Meis homeoproteins in two different organs.

Animals↗

PubMed2006

[Involvement of matrix metalloproteinases in the regulation of myocardial extracellular matrix in patients with congestive heart failure].

OBJECTIVE: To investigate the expression of the matrix metalloproteinases (MMP)-2, -3, and 9, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), fibronectin (FN), and tenascin-C (TN-C) in the myocardium, and their relationship with the myocardial remodeling and heart function in the patients with congestive heart failure (CHF). METHODS: A few tissues of papillary muscles of left ventricle were taken from 39 patients with mitral insufficiency during mitral valve replacement, and from 8 organ donors who had died of accidents to undergo pathological examination and to detect the protein expression of MMP-2, -3, and 9, and TIMP-1 by immunoprecipitation and the expression of FN and TN-C by immunofluorescence test. Peripheral blood samples were collected from these 39 patients and 30 normal controls to examine the plasma MMPs and TIMP-1 by ELISA. RESULTS: Typical myocardial remodeling was seen in the myocardial tissues of the CHF patients. The plasma levels of MMP-2, -3, and -9 of the CHF patients in the cardiac function classes II - IV were all significantly higher than those of the normal controls (P < 0.05 or P < 0.01) with a tendency to increase with the deterioration of heart function, The plasma level of TIMP-1 of the CHF patients in the cardiac function classes II - IV were all significantly higher than that of the normal controls (P < 0.05 or P < 0.01) with a tendency to decrease with the deterioration of heart function. The protein expression levels of MMP-2, -3, and -9 in the myocardium of the CHF patients in the cardiac function classes III - IV were all significantly higher than those of the normal controls (P < 0.05 or P < 0.01) with a tendency to increase with the deterioration of heart function. The protein expression levels of TIMP-1 in the myocardium of the CHF patients in the cardiac function classes III - IV were all significantly lower than that of the normal controls (P < 0.05 or P < 0.01) with a tendency to decrease with the deterioration of heart function. The protein expression levels of FN in the myocardium of the CHF patients in the cardiac function classes II - IV were all significantly lower than that of the normal controls (all P < 0.05) with a tendency to decrease with the deterioration of heart function. The protein expression levels of TN-C in the myocardium of the CHF patients in the cardiac function classes II - IV were all significantly higher than that of the normal controls (all P < 0.01) with a tendency to increase with the deterioration of heart function. CONCLUSION: The increasing expression of MMP-2, -3, and -9 and the decreasing expression of TIMP-1 contribute to the myocardial remodeling, thus changing the extracellular matrix in the myocardium tissue and leading to the development and progression of CHF.

Adult↗

PubMed2006

Differential expression changes in K562 cells during the hemin-induced erythroid differentiation and the phorbol myristate acetate (PMA)-induced megakaryocytic differentiation.

K562 cell line has been used as a model of common progenitor of erythroblasts and magakaryocytes and can be differentiated into erythroid and megakaryocytic lineages by hemin and phorbol myristate acetate (PMA) respectively. We analyzed mRNA expression in un-induced, hemin-induced and PMA-induced K562 cells by differential display reverse transcription polymerase chain reaction (DDRT-PCR) method. 314 differential expression sequence tags (ESTs) were obtained. Among them, 201 ESTs displayed up-regulation and 85 ESTs down-regulation after hemin induction, 186 ESTs showed up-regulation and 72 ESTs down-regulation after PMA induction. The differentially expressed genes included those encoding transcription factors, signaling factors, apoptosis-associated factors and others. 45 of these ESTs stand for genes whose open reading frames were found but whose functions remain unknown. 4 ESTs represent possibly new genes. Furthermore we compared differences of gene expression during hemin-induced erythroid differentiation and PMA-induced megakaryocytic differentiation and found that the expressional changes of some transcription factors and metabolism proteins are the common but the expressional changes of some signal pathways in these two differentiation processes are different. These results suggested that erythroid differentiation and megakaryocytic differentiation are associated in activation and repression of different signal pathways.

Blotting, Northern↗

PubMed2006

Structure of the vesicular stomatitis virus nucleoprotein-RNA complex.

Vesicular stomatitis virus is a negative-stranded RNA virus. Its nucleoprotein (N) binds the viral genomic RNA and is involved in multiple functions including transcription, replication, and assembly. We have determined a 2.9 angstrom structure of a complex containing 10 molecules of the N protein and 90 bases of RNA. The RNA is tightly sequestered in a cavity at the interface between two lobes of the N protein. This serves to protect the RNA in the absence of polynucleotide synthesis. For the RNA to be accessed, some conformational change in the N protein should be necessary.

Amino Acid Sequence↗

PubMed2006

Acoustic quasimodes in two-dimensional dispersed random media.

Using the generalized coherent-potential-approximation approach, we present the dispersion relation of the two-dimensional dispersed random media. In the intermediate-frequency regime, two acoustic modes are found in colloidal suspensions including cylindrical plastic rod in water background. The scattering cross section offers a good explanation for the two modes and the observed frequency gaps in the excitation spectra.

Journal Article↗

PubMed2006

ZBTB34, a novel human BTB/POZ zinc finger protein, is a potential transcriptional repressor.

BTB/POZ protein family plays a key role in many biological processes both in Drosophila and vertebrates through regulating the transcriptional activities of some downstream genes. Here, we obtained a novel member of human BTB/POZ protein family, named as ZBTB34 (Zinc finger and BTB domain containing 34), which encodes 504 amino acid residues with a BTB/POZ domain at its N-terminus that is similar to the same domain of other known transcription regulators. RT-PCR analysis indicated that ZBTB34 was expressed ubiquitously in most adult human tissues, and whilst immunofluorescence assays showed that ZBTB34 was mainly localized to nucleus. Interestingly, the reporter assay in mammalian cells suggested that ZBTB34 might function as a transcriptional repressor. This present work as the first report about the functional exploration of the novel ZBTB34 gene would be contributed to profound understanding of the transcriptional regulation via BTB/POZ protein family.

Amino Acid Sequence↗

PubMed2006

[Protective effect of protein kinase C on heart function: an experiment with isolated rabbit hearts].

OBJECTIVE: To investigate the protective effect of protein kinase C on heart function. METHODS: The hearts of 40 rabbits were isolated, underwent Langendorff perfusion, and randomly divided into 4 equal groups: Group I (control group, the heart underwent long ischemia or preservation for I hour, was re-warmed and re-infused, and then re-perfused with K-H fluid), Group II (ischemic preconditioning group, perfusion was stopped for 5 minutes before the long ischemia, then the aorta was re-infused), Group III (specific activator of PKC, phorbol myristate acetate was infused inversely via the aorta before the perfusion of K-H fluid), and Group IV (polymyxin B, a specific antagonist of PKC, was infused after the infusion of PKC). Before the preservation and by the end of reperfusion left ventricle end systolic pressure (LVESP), and left ventricle end diastolic pressure (LVDSP) were measured. At the end of experiment specimens of myocardium were collected from each heart to measure the water content, the levels of lactic dehydrogenase and MB isoenzyme of creatine kinase (CK-MB), superoxide dismutase (SOD), and malonyldialdehyde (MDA). TUNEL method was used to measure the number of apoptotic cardiomyocyte. RESULTS: All heart resumed beating. The LVESP of Group II and III were both significantly higher than those of Groups I and IV (all P < 0.05) and the LVESP of Group III was significantly higher than that of Group II too (P < 0.05). The LVEDP of Group II and III were both significantly lower than those of Groups I and IV (all P < 0.05) and the LVEDP of Group III was significantly lower than that of Group II too (P < 0.05). The levels of CK-MB, LDH, and SOD of Group II and III were all significantly higher than those of Groups I and IV (all P < 0.05) and the levels of CK-MB and LDH of Group III was significantly higher than that of Group II too (P < 0.05). The level of MDA of Group II and III were both significantly lower than those of Groups I and IV (all P < 0.05) and the level of MDA of Group III was significantly lower than that of Group II too (P < 0.05). The water contents of Group II and III were both significantly lower than those of Groups I and IV (all P < 0.05). The numbers of TUNEL positive cell and apoptotic cells of Group II and III were all significantly lower than those of Groups I and IV (all P < 0.05). CONCLUSIONS: PKC can be activated by transient ischemia and PMA. PKC protects the heart function effectively.

Animals↗

PubMed2006

New perspectives on host-parasite interplay by comparative transcriptomic and proteomic analyses of Schistosoma japonicum.

Schistosomiasis remains a serious public health problem with an estimated 200 million people infected in 76 countries. Here we isolated ~ 8,400 potential protein-encoding cDNA contigs from Schistosoma japonicum after sequencing circa 84,000 expressed sequence tags. In tandem, we undertook a high-throughput proteomics approach to characterize the protein expression profiles of a number of developmental stages (cercariae, hepatic schistosomula, female and male adults, eggs, and miracidia) and tissues at the host-parasite interface (eggshell and tegument) by interrogating the protein database deduced from the contigs. Comparative analysis of these transcriptomic and proteomic data, the latter including 3,260 proteins with putative identities, revealed differential expression of genes among the various developmental stages and sexes of S. japonicum and localization of putative secretory and membrane antigens, enzymes, and other gene products on the adult tegument and eggshell, many of which displayed genetic polymorphisms. Numerous S. japonicum genes exhibited high levels of identity with those of their mammalian hosts, whereas many others appeared to be conserved only across the genus Schistosoma or Phylum Platyhelminthes. These findings are expected to provide new insights into the pathophysiology of schistosomiasis and for the development of improved interventions for disease control and will facilitate a more fundamental understanding of schistosome biology, evolution, and the host-parasite interplay.

Amino Acid Sequence↗

PubMed2006

Global landscape of protein complexes in the yeast Saccharomyces cerevisiae.

Identification of protein-protein interactions often provides insight into protein function, and many cellular processes are performed by stable protein complexes. We used tandem affinity purification to process 4,562 different tagged proteins of the yeast Saccharomyces cerevisiae. Each preparation was analysed by both matrix-assisted laser desorption/ionization-time of flight mass spectrometry and liquid chromatography tandem mass spectrometry to increase coverage and accuracy. Machine learning was used to integrate the mass spectrometry scores and assign probabilities to the protein-protein interactions. Among 4,087 different proteins identified with high confidence by mass spectrometry from 2,357 successful purifications, our core data set (median precision of 0.69) comprises 7,123 protein-protein interactions involving 2,708 proteins. A Markov clustering algorithm organized these interactions into 547 protein complexes averaging 4.9 subunits per complex, about half of them absent from the MIPS database, as well as 429 additional interactions between pairs of complexes. The data (all of which are available online) will help future studies on individual proteins as well as functional genomics and systems biology.

Biological Evolution↗

PubMed2006

[Percutaneous nephrolithotripsy with pneumatic and ultrasonic power under B-type ultrasound guidance for treatment of renal calculi in non-dilated collecting system].

OBJECTIVE: To evaluate the efficacy and safety of management of renal stone in non-dilated collecting system by percutaneous nephrolithotripsy (PCNL) under ultrasound guidance. METHOD: From September 2003 to April 2005, 132 cases of renal stone in non-dilated collecting system were performed by percutaneous nephrolithotripsy. A stent was first inserted into the pelvis through cystoscope, and saline was instilled to dilate collecting system. Antegrade percutaneous access was obtained by B-type ultrasound guidance. A combination pneumatic and ultrasonic lithotrite were used to disintegrate and remove stone under direct vision. Clinical data including operation time, complications and stone free rate were analyzed retrospectively. RESULTS: The percutaneous renal access was successfully established under B-type ultrasound guidance in all patients, immediate phase I lithotripsy was performed in 129 cases and delayed phase II lithotripsy in 3 cases. Operation time ranged from 70 to 130 minutes, average time was (89 +/- 11) minutes, 3 cases were supported by blood transfusion, severe complications did not occur during nephrolithotripsy. Stones were cleared in 114 out of 132 cases (86.4%) during immediate phase I lithotripsy, residual stone fragment was found in 18 cases who received second PCNL or adjuvant extracorporeal shock wave lithotripsy. CONCLUSION: The management of renal stone in non-dilated collecting system using PCNL appears to be efficacious and safe under B-type ultrasound guidance.

Adult↗

PubMed2006

Separation of Delta5- and Delta7-phytosterols by adsorption chromatography and semipreparative reversed phase high-performance liquid chromatography for quantitative analysis of phytosterols in foods.

A method for the separation, isolation, and identification of phytosterols was developed. A commercial phytosterols mixture, Generol 95S, was fractionated first by adsorption silica gel column chromatography and then separated by means of a semipreparative reverse phase high-performance liquid chromatography fitted with a Polaris C8-A column (250 mm x 10 mm i.d., 5 microm) using isocratic acetonitrile:2-propanol:water (2:1:1, v/v/v) as the mobile phase. Milligram scales of six individual phytosterols, including citrostadienol, campesterol, beta-sitosterol, Delta7-avenasterol, Delta7-campesterol, and Delta7-sitosterol, were obtained. Purities of these isolated sterols were 85-98%. Relative response factors (RRF) of these phytosterols were calculated against cholestanol as an authentic commercial standard. These RRF values were used to quantify by gas chromatography-mass spectrometry (GC-MS) the phytosterols content in a reference material, oils, and chocolates.

Adsorption↗

PubMed2006

Extremely low penetrance of deafness associated with the mitochondrial 12S rRNA mutation in 16 Chinese families: implication for early detection and prevention of deafness.

Mutations in mitochondrial DNA (mtDNA) have been found to be associated with sensorineural hearing loss. We report here the clinical, genetic, and molecular characterization of 16 Chinese pedigrees (a total of 246 matrilineal relatives) with aminoglycoside-induced impairment. Clinical evaluation revealed the variable phenotype of hearing impairment including audiometric configuration in these subjects, although these subjects share some common features: being bilateral and sensorineural hearing impairment. Strikingly, these Chinese pedigrees exhibited extremely low penetrance of hearing loss, ranging from 4% to 18%, with an average of 8%. In particular, nineteen of 246 matrilineal relatives in these pedigrees had aminoglycoside-induced hearing loss. Mutational analysis of the mtDNA in these pedigrees showed the presence of homoplasmic 12S rRNA A1555G mutation, which has been associated with hearing impairment in many families worldwide. The extremely low penetrance of hearing loss in these Chinese families carrying the A1555G mutation strongly supports the notion that the A1555G mutation itself is not sufficient to produce the clinical phenotype. Children carrying the A1555G mutation are susceptible to the exposure of aminoglycosides, thereby inducing or worsening hearing impairment, as in the case of these Chinese families. Using those genetic and molecular approaches, we are able to diagnose whether children carry the ototoxic mtDNA mutation. Therefore, these data have been providing valuable information and technology to predict which individuals are at risk for ototoxicity, to improve the safety of aminoglycoside therapy, and eventually to decrease the incidence of deafness.

Adolescent↗

PubMed2006

Potential role of short hairpin RNA targeting epidermal growth factor receptor in growth and sensitivity to drugs of human lung adenocarcinoma cells.

Upregulation of expression and activation of epidermal growth factor receptor (EGFR) is involved in the development and progression of a wide range of human cancers. The present study aims at determining gene-silencing effects of vector-based short hairpin RNA (shRNA) targeting EGFR on receptor expression and cell growth and evaluating its modulation of responsiveness to drugs in human lung adenocarcinoma cells (HLAC). A vector-based polymerase 3-promotor system was used to express shRNA targeting EGFR in HLAC lines (A549 and SPC-A1). EGFR was detected by immunofluorescence staining and quantified by Western blot. The effect of shRNA targeting EGFR on tumor cell growth was assessed by colony formation assay, cell cycle and apoptosis by flow cytometry, and the responsiveness of HLAC lines to cytotoxic drugs by 3-[4,5-dimethylthiozol-2yl]-2,5-diphenyltetrazolium bromide [MTT] assay. Vectors expressing shRNA against EGFR significantly downregulated receptor expression by 74 and 85% and the colony number by 63 and 69% in A549 and SPC-A1, respectively. Vector-based shRNA against EGFR caused G1 arrest, induced apoptosis, and subsequently increased the sensitivity to cisplatin, doxorubicin and paclitaxel by about four- to seven-fold in both HLAC lines. Our data suggest that vector-based shRNA could be considered as an alternative to effectively inhibit EGFR expression in HLACs, probably with the higher efficacy in combination therapies with conventional chemotherapeutic drugs.

Adenocarcinoma↗

PubMed2006

Evaluation of poly{-N-isopropylacrylamide-co-[3-(methacryloylamino)propyl]trimethylammonium} as a stationary phase for capillary electrochromatography.

A cationic polyacrylamide-based stationary phase was synthesized and characterized for CEC. The stationary phase was prepared by radical copolymerization of N-isopropylacrylamide (NIPAAm) and (3-(methacryloylamino)propyl)trimethylammonium chloride (MAPTA), producing a copolymer attached to 5 microm porous silica particles. Fourier transform infrared spectroscopy and thermogravimetric analysis were used to characterize the copolymer. Under capillary electrochromatographic conditions, the poly-NIPAAm-co-MAPTA stationary phase showed to be stable in a wide pH range. The amino groups in the MAPTA provided an anodic EOF for CEC separation. The electroosmotic mobility changed less than 10% when the pH of the mobile phase was changed from 2 to 12. The run-to-run RSD of analyte migration time was less than 1.5% (n = 3), and the RSD of peak area was less than 3% (n = 3). The day-to-day RSD for migration time was less than 2% (n = 3). The polar groups present in the stationary phase contributed to the selectivity of the phase providing for hydrophilic interactions. In the separation of a series of neutral and acidic compounds, the stationary phase shows a mixed-mode separation mechanism with both hydrophobicity and hydrophilicity contributing to the separation.

Acrylamides↗

PubMed2006

Insights into human CD34+ hematopoietic stem/progenitor cells through a systematically proteomic survey coupled with transcriptome.

Hematopoietic stem cells are capable of self-renewal and differentiation into different hematopoietic lineages. To gain a comprehensive understanding of hematopoietic stem/progenitor cells, a systematic proteomic survey of human CD34+ cells collected from human umbilical cord blood was performed, in which the proteins were separated by 1- and 2-DE, as well as by nano-LC, and subsequently identified by MS. A total of 370 distinct proteins identified from those cells provided new insights into the potential of the stem/progenitor cells because the nerve, gonad, and eye-associated proteins were reliably identified. Interestingly, the transcripts of 133 (35.9%) identified proteins were not found by the prevalent transcriptome approaches, although several selected transcripts could be detected by RT-PCR. Moreover, the heterogeneity of 33 proteins identified from 2-DE was attributable primarily to post-translational processes rather than to alternative splicing at transcriptional level. Furthermore, the biosyntheses of 15 proteins identified in this study appears not to be completely interrupted in spite of the fact that corresponding antisense RNAs were found in the existing transcriptome data. The integrated proteomic and transcriptomic analyses employed here provided a unique view of the human stem/progenitor cells.

Antigens, CD34↗

PubMed2006

The nonspecific anti-inflammatory therapy with methotrexate for patients with chronic heart failure.

BACKGROUND: Inflammatory mediators play an important role in the pathogenesis of chronic heart failure (CHF). Methotrexate (MTX) is used in the treatment of inflammatory-mediated diseases (eg, rheumatoid arthritis) because it modulates the expression of numerous inflammatory cytokines. However, no studies have assessed the effects of MTX on plasma levels of inflammatory mediators in patients with CHF. METHODS: In a prospective, randomized, placebo-controlled, single-blind study, 71 patients receiving conventional treatment were randomly allocated to either MTX group (7.5 mg once a week, n = 35) or placebo group (n = 36) with a follow-up of 12 weeks. The effects of MTX on plasma cytokine expression, left ventricular ejection fraction, left ventricular end-diastolic dimension, New York Heart Association (NYHA) functional class, 6-minute walk test distance, and quality of life (QOL) were determined in patients with CHF. RESULTS: Sixty-two patients completed the study. The circulating levels of inflammatory mediators in patients with CHF were markedly elevated compared with healthy controls (P < or = .002). Methotrexate (n = 30) reduced plasma levels of tumor necrosis factor alpha (-15.6%, P < .05), interleukin 6 (-21.8%, P < .01), monocyte chemoattractant protein-1 (-22.6%, P < .01), soluble intercellular adhesion molecule-1 (-19.2%, P < .05), and C-reactive protein (-27.2%, P < .01) compared with baseline. Furthermore, interleukin 10 (15.8 %, P < .05) and soluble IL-1 receptor antagonist (36.1%, P < .01) expression was increased, whereas improvements in NYHA classification, 6-minute walk test distance, and QOL were found compared with baseline. Monocyte chemoattractant protein-1 expression was lower and soluble IL-1 receptor antagonist expression higher in the MTX than placebo group (n = 32). Furthermore, the left ventricular ejection fraction, left ventricular end-diastolic dimension, and incidence of main adverse cardiac events between the 2 groups were similar. CONCLUSION: These results suggest that the addition of MTX to conventional therapy for CHF has significant anti-inflammatory effects and improves NYHA functional class, 6-minute walk test distance, and QOL.

Anti-Inflammatory Agents↗