Construction of an oxidative stress-associated genes signature in breast cancer by machine learning algorithms.

OBJECTIVE: To construct a prognostic model of a breast cancer-related oxidative stress-related gene (OSRG) signature using machine learning algorithms. METHODS: The OSRGs of breast cancer were constructed by least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analysis. The Cancer Genome Atlas (TCGA) was used to analyse the gene expression and prognostic value. The Human Protein Atlas was used to analyse the protein expression of hub genes. Receiver operating characteristic analysis, calibration curve and decision curve analysis were used to predict the stability of this model. RESULTS: The area under the curve of 1-, 3- and 5-year overall survival were 0.751, 0.707 and 0.645 in the TCGA training dataset; and 0.692, 0.678 and 0.602 in the TCGA testing dataset, respectively. Calibration plot showed good agreement between predicted probabilities and observed outcomes. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA) pathway analysis indicated that multiple cancer-related pathways were highly enriched in the high-risk group. Immune infiltration analysis showed immune cells and their functions may play a key role in the development and mechanism of breast cancer. CONCLUSIONS: This new OSRG signature was associated with the immune infiltration and it might be useful in predicting the prognosis in patients with breast cancer.

Association between Urinary Lead and Female Breast Cancer: A Population-Based Cross-Sectional Study.

BACKGROUND: Previous studies have explored the relationship between serum lead levels and the risk of female breast cancer (FBC). However, it is still uncertain whether urinary lead levels are associated with FBC. This study aimed to investigate the potential association between urinary lead and FBC. METHODS: A cross-sectional case-control study was conducted using the National Health and Nutrition Examination Survey (NHANES), which is a series of cross-sectional, nationally representative surveys of the United States population consisting of 10 survey waves from 1999 to 2018. This study analyzed a total of 2795 female participants (≥20 years), consisting of 210 participants with FBC and 2585 healthy controls. Urinary lead was detected using Inductively Coupled Plasma-Mass Spectrometry, which was divided into four levels by using quartiles-defining cut points. Multivariate logistic regression was used to analyze the association between urinary lead and FBC. RESULTS: Multivariate logistic regression revealed that urinary lead was positively correlated with FBC (Odds ratio [OR], 2.16; 95% confidence interval [CI]: [1.18, 3.95], p < 0.05) in a fully adjusted model. There were significantly increased ORs of FBC in quartile 4 (Q4) and quartile 3 (Q3), compared with the lowest quartile 1 (Q1) (Q4, OR = 1.48, 95% CI [0.89, 2.48]; Q3: OR = 1.01, 95% CI [0.59, 1.73], p for trend = 0.021). No significant interaction effects were observed between urinary lead levels and FBC between the subgroups (age, race, educational status, body mass index (BMI), marital status, family income to poverty ratio, hypertension status, diabetes status, renal function status, smoking history, ever been pregnant, oral contraceptive use, occupation classification, etc.) (All interaction p-value > 0.05). CONCLUSIONS: Urinary lead is likely positively associated with FBC in the US population.

Structural basis for the self-recognition of sDSCAM in Chelicerata.

To create a functional neural circuit, neurons develop a molecular identity to discriminate self from non-self. The invertebrate Dscam family and vertebrate Pcdh family are implicated in determining synaptic specificity. Recently identified in Chelicerata, a shortened Dscam (sDscam) has been shown to resemble the isoform-generating characters of both Dscam and Pcdh and represent an evolutionary transition. Here we presented the molecular details of sDscam self-recognition via both trans and cis interactions using X-ray crystallographic data and functional assays. Based on our results, we proposed a molecular zipper model for the assemblies of sDscam to mediate cell-cell recognition. In this model, sDscam utilized FNIII domain to form side-by-side interactions with neighboring molecules in the same cell while established hand-in-hand interactions via Ig1 domain with molecules from another cell around. Together, our study provided a framework for understanding the assembly, recognition, and evolution of sDscam.

Adiponectin and the risk of gastrointestinal cancers in East Asians: Mendelian randomization analysis.

BACKGROUND: Adiponectin is an important adipocytokine and has been associated with the risks of gastrointestinal cancers (GICs). Mendelian randomization (MR) analysis is needed to assess the causal relationships between adiponectin and GICs. METHODS: We retrieved the summary data of genome-wide association studies for adiponectin and six types of GICs in East Asians. A series of quality control steps were performed to select the eligible genetic instrumental tools. Horizontal pleiotropy and between-SNP heterogeneity were tested to choose the primary MR method. We also conducted sensitivity analyses to test the robustness of the main findings. RESULTS: We detected neither heterogeneity nor horizontal pleiotropy for the eligible SNPs in all of the MR analyses. Inverse variance weighted (IVW) was therefore used as the primary method, and suggested that per 10% increase in log-transformed adiponectin level was significantly associated with a decreased risk of gastric cancer (odds ratio [OR] = 0.88, 95% CI 0.81, 0.96), whereas with an increased risk of hepatocellular carcinoma (OR = 1.26, 95% CI 1.09, 1.44) and of biliary tract cancer (OR = 1.54, 95% CI 1.12, 2.12). However, only the association between adiponectin and HCC risk was statistically significant after correction for multiple testing. No statistically significant association was detected between adiponectin and esophageal (OR = 1.05, 95% CI 0.89, 1.23), pancreatic (OR = 1.04, 95% CI 0.78, 1.37), and colorectal cancers (OR = 1.00, 95% CI 0.93, 1.07). Sensitivity analyses did not find contradictory results. CONCLUSION: High level of adiponectin may have a causal effect on and can serve as a biomarker for the carcinogenesis of gastric cancer, hepatocellular carcinoma, and biliary tract cancer.

Deciphering the Oncogenic Role of VPS28 Modulated by miR-491-5p in Breast Cancer Cells Using In Silico and Functional Analysis.

Vacuolar protein sorting-associated protein 28 (VPS28), one of the four cytosolic proteins comprising the endosomal sorting complex required for the transport I (ESCRT-I) component, has been reported to be linked to various cancers. However, less evidence is available regarding the involvement of VPS28 in breast cancer. To this end, this study focused on exploring the function of VPS28 in breast cancer cells using the in silico analysis. VPS28 expression pattern data in breast cancer tissues were collected using the Cancer Genome Atlas (TCGA) and Clinical Proteomic Tumor Analysis Consortium (CPTAC) databases and analyzed to assess the association of VPS28 with breast cancer prognosis. The elevated VPS28 expression was found in breast cancer tissues and was associated with a poor prognosis (p < 0.001). A higher VPS28 expression indicated a short survival duration (HR = 2.43; 95% CI: 1.44-4.1; p < 0.001). The CCLE database showed that VPS28 was expressed in breast cancer cell lines. The upstream targets of VPS28 were identified using the mirDIP, starBase, and TargetScan online tools. The correlation and binding relationship between miR-491-5p and VPS28 was analyzed. VPS28 or miR-491-5p gain and loss of function experiments were performed to verify their potential effect on the biological functions of breast cancer cells. Knockdown of VPS28 was shown to suppress the biological functions and enhance the apoptosis of breast cancer cell lines. Micro RNA-491-5p, identified as a posttranscriptional regulator of VPS28, was downregulated in breast cancer tissues. In contrast to the miR-491-5p inhibitor, the miR-491-5p mimic could suppress the migration, wound healing ability, and proliferation, while accelerating apoptosis. However, co-transfection of VPS28 and miR-491-5p counteracted the effect of the miR-491-5p mimic on breast cancer cell functions. Thus, our in silico analysis demonstrates that miR-491-5p can suppress breast cancer progression by attenuating the expression of VPS28.

Mechanisms of spacer acquisition by sequential assembly of the adaptation module in Synechocystis.

CRISPR-Cas immune systems process and integrate short fragments of DNA from new invaders as spacers into the host CRISPR locus to establish molecular memory of prior infection, which is also known as adaptation in the field. Some CRISPR-Cas systems rely on Cas1 and Cas2 to complete the adaptation process, which has been characterized in a few systems. In contrast, many other CRISPR-Cas systems require an additional factor of Cas4 for efficient adaptation, the mechanism of which remains less understood. Here we present biochemical reconstitution of the Synechocystis sp. PCC6803 type I-D adaptation system, X-ray crystal structures of Cas1-Cas2-prespacer complexes, and negative stained electron microscopy structure of the Cas4-Cas1 complex. Cas4 and Cas2 compete with each other to interact with Cas1. In the absence of prespacer, Cas4 but not Cas2 assembles with Cas1 into a very stable complex for processing the prespacer. Strikingly, the Cas1-prespacer complex develops a higher binding affinity toward Cas2 to form the Cas1-Cas2-prespacer ternary complex for integration. Together, we show a two-step sequential assembly mechanism for the type I-D adaptation module of Synechocystis, in which Cas4-Cas1 and Cas1-Cas2 function as two exclusive complexes for prespacer processing, capture, and integration.

Altered Serum Annexin A2 Might Be a New Potential Diagnostic Biomarker in Human Colorectal Cancer.

OBJECTIVE: Annexin A2 is a calcium dependent phospholipid binding protein that is a biomarker in cancers. However, the value of serum Annexin A2 in the diagnosis of colorectal cancer (CRC) is not clear. This study aimed to investigate clinical utility of serum Annexin A2 as a potential biomarker for CRC. METHODS: Annexin A2 was analyzed in 20 cases of CRC tissues and 20 controls of normal adjacent paired tissues. Serum Annexin A2 was calculated in 59 CRC patients and 44 healthy subjects. Receiver operating characteristic (ROC) curve and logistic regression were utilized to evaluate the diagnostic effectiveness and construct diagnostic model. RESULTS: Annexin A2 in CRC tissues was slightly higher than in normal adjacent paired tissues (χ2=6.0652, p<0.05). Serum Annexin A2 in CRC patients was significantly lower than in healthy controls (p<0.05). Besides, the levels of serum Annexin A2 were lower in patients with poor tumor differentiation than in well or moderate tumor differentiation (p=0.0111). ROC analysis indicated the diagnostic efficacy of serum Annexin A2 was better than carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA199) for CRC. Furthermore, joint detection of Annexin A2 and CEA had the maximum area under the ROC curve (AUC) in discriminating CRC from healthy controls (AUC 0.931, sensitivity 86.4%, specificity 84.7%, positive predictive value 87.9%, and negative predictive value 82.2%). CONCLUSIONS: Serum Annexin A2 may be a non-invasive and promising biomarker for the diagnosis of CRC, and the joint detection of Annexin A2 and CEA may have been favorable clinical applied value in the diagnosis of CRC.

Five-mRNA Signature for the Prognosis of Breast Cancer Based on the ceRNA Network.

BACKGROUND: The purpose of this study was to investigate the regulatory mechanisms of ceRNAs in breast cancer (BC) and construct a new five-mRNA prognostic signature. METHODS: The ceRNA network was constructed by different RNAs screened by the edgeR package. The BC prognostic signature was built based on the Cox regression analysis. The log-rank method was used to analyse the survival rate of BC patients with different risk scores. The expression of the 5 genes was verified by the GSE81540 dataset and CPTAC database. RESULTS: A total of 41 BC-adjacent tissues and 473 BC tissues were included in this study. A total of 2,966 differentially expressed lncRNAs, 5,370 differentially expressed mRNAs, and 359 differentially expressed miRNAs were screened. The ceRNA network was constructed using 13 lncRNAs, 267 mRNAs, and 35 miRNAs. Kaplan-Meier (K-M) methods showed that two lncRNAs (AC037487.1 and MIR22HG) are related to prognosis. Five mRNAs (VPS28, COL17A1, HSF1, PUF60, and SMOC1) in the ceRNA network were used to establish a prognostic signature. Survival analysis showed that the prognosis of patients in the low-risk group was significantly better than that in the high-risk group (p = 0.0022). ROC analysis showed that this signature has a good diagnostic ability (AUC = 0.77). Compared with clinical features, this signature was also an independent prognostic factor (HR: 1.206, 95% CI 1.108-1.311; p < 0.001). External verification results showed that the expression of the 5 mRNAs differed between the normal and tumour groups at the chip and protein levels (p < 0.001). CONCLUSIONS: These ceRNAs may play a key role in the development of BC, and the new 5-mRNA prognostic signature can improve the prediction of survival for BC patients.

Less expression of CD4+ and CD8+ T cells might reflect the severity of infection and predict worse prognosis in patients with COVID-19: Evidence from a pooled analysis.

This study mainly focused on the very serious COVID-19 epidemic situation at present and provided a new insight for the treatment and monitor of patients with COVID-19. Through this meta-analysis, we could draw a conclusion that less expression of blood CD4+ and CD8+ T cells count might reflect the severity of infection and often accompanied by a poor prognosis. Hence, we inferred blood CD4+ and CD8+ T cells count could be a promising biomarker for disease assessment and monitor of patients with COVID-19.

Identification of prognostic biomarkers and drug target prediction for colon cancer according to a competitive endogenous RNA network.

Colorectal cancer is one of the commoner digestive tract malignant tumor types, and its incidence and mortality rate are high. Accumulating evidence indicates that long­chain non­coding RNAs (lncRNAs) and protein­coding RNAs interact with each other by competing with the same micro(mi)RNA response element (MREs) and serve an important role in the regulation of gene expression in a variety of tumor types. However, the regulatory mechanism and prognostic role of lncRNA­mediated competing endogenous (ce)RNA networks in colon cancer have yet to be elucidated. The expression profiles of mRNAs, lncRNAs and miRNAs from 471 colon cancer and 41 paracancerous tissue samples were downloaded from The Cancer Genome Atlas database. A lncRNA­miRNA­mRNA ceRNA network in colon cancer was constructed and comprised 17 hub lncRNAs, 87 hub miRNA and 144 hub mRNAs. The topological properties of the network were analyzed, and the random walk algorithm was used to identify the nodes significantly associated with colon cancer. Survival analysis using the UALCAN database indicated that 2/17 lncRNAs identified [metastasis­associated lung adenocarcinoma transcript (MALAT1) and maternally expressed gene 3 (MEG3)] and 5/144 mRNAs [FES upstream region (FURIN), nuclear factor of activated T­cells 5 (NFAT5), RNA Binding Motif Protein 12B (RBM12B), Ras related GTP binding A (RRAGA) and WD repeat domain phosphoinositide­interacting protein 2 (WIPI2)] were significantly associated with the overall survival of patients with colon cancer, and may therefore be used as potential prognostic biomarkers of colon cancer. According to extracted lncRNA­miRNA­mRNA interaction pairs, the GSE26334 dataset was used to confirm that the lncRNA MALAT1/miR­129­5p/NFAT5 axis may represent a novel regulatory mechanism concerning the progression of colon cancer. The clusterProfiler package was used to analyze Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways in colon cancer. Finally, drugs that significantly interact with the core genes identified in colon cancer were predicted using a hypergeometric test. Of these, fostamatinib was identified to be a targeted drug for colon cancer therapy. The present findings provide a novel perspective for improved understanding of the lncRNA­associated ceRNA network and may facilitate the development of novel targeted therapeutics in colon cancer.

Structural insights into the design of indole derivatives as tubulin polymerization inhibitors.

Microtubules are composed of αß-tubulin heterodimers, and drugs that interfere with microtubule dynamics are used widely in cancer chemotherapy. Small synthetic molecules with an indole nucleus as a core structure have been identified as microtubule inhibitors and recognized as anticancer agents. However, structural information for the interactions between indole derivatives and tubulin is sparse. Here, we present the 2.55 Å crystal structure of tubulin in complex with the indole derivative D64131. We compare the binding modes of D64131, colchicine, and five other indole derivatives to tubulin. These results reveal the interactions between the indole derivatives and tubulin, explain previous results of structure-activity-relationship (SAR) studies and, thus, provide insights into the development of new indole derivatives targeting the colchicine binding site.

High WDR34 mRNA expression as a potential prognostic biomarker in patients with breast cancer as determined by integrated bioinformatics analysis.

The WD-repeat domain (WDR) family is distributed in the majority of eukaryotes and has several unique biological functions. It serves important roles in signal transduction, cytoskeleton assembly, protein transport, RNA processing, chromatin modification and transcription mechanisms. WD repeat domain 34 (WDR34) has been recently identified as a member of the WDR family. Overexpression of WDR34 was accompanied by the presence of multiple centrioles in the cell, suggesting that it was associated with tumor occurrence. However, its association with breast cancer was unclear. To the best of our knowledge, it has not yet been confirmed whether WDR34 gene expression is associated with breast cancer. Therefore, the current study attempted to clarify this by performing a comprehensive study using multiple datasets in the Oncomine, Breast Cancer Gene-Expression Miner and Kaplan-Meier Plotter databases. The analysis indicated that the mRNA expression levels of WDR34 were increased in breast cancer tissues compared with normal tissues. Consistent with this result, the Broad-Novartis Cancer Cell Line Encyclopedia revealed that WDR34 mRNA expression levels were upregulated in breast cancer cell lines compared with other cancer cells. It was noted that high WDR34 mRNA expression was associated with forkhead box M1 and PTTG1 regulator of sister chromatid separation, securing in co-expression analysis. Expression profile characteristics of WDR34 mRNA were identified in different molecular subtypes of breast cancer. Furthermore, survival analysis revealed that increased expression levels of WDR34 mRNA were associated with poor overall survival in patients with breast cancer, particularly in luminal B, lymph node status-positive and estrogen receptor (ER)-negative subgroups. Additionally, Kaplan-Meier curves revealed that high WDR34 mRNA expression was associated with shorter relapse-free survival in patients with breast cancer, particularly in ER-positive, human epidermal growth factor receptor 2-negative and progesterone receptor-positive subgroups. These results suggested that WDR34 may be used as a prognosis predictor in breast cancer and may provide a novel target for the diagnosis and treatment of breast cancer.

A Mendelian Randomization Study of Plasma Homocysteine and Multiple Myeloma.

Observational studies have demonstrated an association between elevated homocysteine (Hcy) level and risk of multiple myeloma (MM). However, it remains unclear whether this relationship is causal. We conducted a Mendelian randomization (MR) study to evaluate whether genetically increased Hcy level influences the risk of MM. We used the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism as an instrumental variable, which affects the plasma Hcy levels. Estimate of its effect on plasma Hcy level was based on a recent genome-wide meta-analysis of 44,147 individuals, while estimate of its effect on MM risk was obtained through meta-analysis of case-control studies with 2,092 cases and 4,954 controls. By combining these two estimates, we found that per one standard-deviation (SD) increase in natural log-transformed plasma Hcy levels conferred a 2.67-fold increase in risk for MM (95% confidence interval (CI): 1.12-6.38; P = 2.7 × 10(-2)). Our study suggests that elevated Hcy levels are causally associated with an increased risk of developing MM. Whether Hcy-lowering therapy can prevent MM merits further investigation in long-term randomized controlled trials (RCTs).

[Epidemiological analysis of malaria situation in Shuyang County, Jiangsu Province from 2004 to 2013].

OBJECTIVE: To understand the epidemic situation and prevalent characteristics of malaria in Shuyang County, Jiangsu Province from 2004 to 2013, so as to provide the references for formulating effective strategies and measures of malaria control. METHODS: The reported epidemic situation and epidemiological data of malaria were collected and analyzed in Shuyang County from 2004 to 2013. RESULTS: Totally 31 malaria cases were reported with an incidence rate of 0.18/100 000 in Shuyang County, from 2004 to 2013, of which 22 were local cases and 9 were imported cases. The peak season of local infection cases were during August and October. The infectors were mainly men and the sex ratio was 2.87:1. The age group from 10 to 39 years had the highest incidence. CONCLUSION: The focus of infection situation of malaria in Shuyang County is changing from local cases to imported cases. The management of floating population and training and publicity concerned with imported malaria should be strengthened.

Gardiquimod inhibits the expression of calcium-induced differentiation markers in HaCaT cells.

Toll-like receptor 7 (TLR7) is an important member in pattern recognition receptors families. TLR7 signal pathway is involved in the physiological process in many type cells, but the impact of TRL7 on differentiation in the human keratinocytes is still unknown. In this study, we investigated the expression of TLR7 in keratinocytes, and the effect of TLR7 agonist gardiquimod on the expression of calcium (Ca(2+))-induced keratinocytes differentiation markers in HaCaT cells. Immunohistochemistry and western-blotting analysis showed that TLR7 is expressed in basal keratinocytes of normal skin and in the human keratinocyte cell line HaCaT, but not expressed in the keratinocytes of psoriasis lesions. Pretreatment with gardiquimod could down-regulate Ca(2+)-induced differentiation marker expression and activate Raf-MEK-ERK and PI3K-AKT signal pathways in HaCaT cells. However, specific inhibitors studies showed that the down-regulation of the differentiation markers expression by gardiquimod was not dependent on the activation of these two pathways. TLR7 may play an important role in the pathogenesis of psoriasis through regulating the differentiation of the keratinocytes, and will give a new insight into the psoriasis.

Interleukin 29 enhances expression of Toll receptor 3 and mediates antiviral signals in human keratinocytes.

OBJECTIVE: Interleukin 29 (IL-29) is a class II cytokine and displays numerous immune functions other than its anti-viral and antiproliferation activities. This study is focused on the effect of IL-29 on human keratinocytes (KCs). METHODS: Primary KCs were stimulated by various concentrations of IL-29 for different time periods, and antiviral proteins and TLR3 gene expression were then analyzed by real-time PCR. The signal pathways activated by IL-29 in KCs were detected by western blot. The antiviral activity of IL-29 was determined by methylthiazolyldiphenyl-tetrazolium bromide, and small interfering RNA knockdown was used to analyze the role of toll receptor 3 (TLR3) in the antiviral activity of IL-29. RESULTS: IL-29 was able to induce expression of antiviral proteins and TLR3 gene expression in KCs. IL-29 pretreatment strongly enhanced herpes simplex virus type 1 (HSV-1)-induced expression of the interferon ß (IFN-ß) gene and protected the KCs from HSV-1 challenge. The IL-29 antiviral activity was partially dependent on TLR3 expression induced by this cytokine, and mechanistic studies demonstrated that the regulation of TLR3 expression by IL-29 might be partially dependent on Janus kinase /signal transducer and activator of transcription (JAK-STATs) activation. CONCLUSION: IL-29-induced TLR3 expression is involved in antiviral activity of IL-29 in KCs, which suggests a feasible method to cure certain viral infections of the skin.

IL-29 and IFN-α regulate the expression of MxA, 2',5'-OAS and PKR genes in association with the activation of Raf-MEK-ERK and PI3K-AKT signal pathways in HepG2.2.15 cells.

Interferons (IFNs) can activate the PI3K-AKT and Raf-MEK-ERK signal pathways and induce antiviral proteins (MxA, 2',5'-OAS and PKR) expression in specific cell lines. However, the relationship between those antiviral proteins expression and signal pathways remains unknown at present. Thus our experiments were designed to determine the exact relationship in HepG2.2.15 cell line. The results demonstrated that IFN-α and IL-29 were both able to activate PI3K-AKT and Raf-MEK-ERK signal pathways, and IFN-α up-regulated the expression of MxA, 2',5'-OAS and PKR whereas IL-29 increased mRNA expression of MxA and 2',5'-OAS and had no influence on PKR. Furthermore, MxA, 2',5'-OAS and PKR expression were down-regulated while PI3K-AKT signal pathway was blocked by LY294002. And MxA was up-regulated after Raf-MEK-ERK signal pathway being blocked by PD98059. These findings indicate that the expression of MxA, 2',5'-OAS and PKR are up-regulate by PI3K-AKT signal pathway, and Raf-MEK-ERK signal pathway has a negative regulatory effect on the expression of MxA and no significant effect on 2',5'-OAS and PKR.

[N-acetylcysteine antagonizes the Interleukin-18-induced expression of TNF-alpha and IL-6 in mouse vascular smooth muscle cells].

AIM: To explore the effect of N-acetylcysteine(NAC)on the interleukin(IL)18-induced expression of tumor necrosis factor (TNF) alpha and interleukin(IL) 6 in mouse vascular smooth muscle cells(VSMC). METHODS: VSMC was stimulated with various concentrations of IL-18 for different times after addition of NAC(5 mmol/L) for 1 h. The messenger ribonucleic acid(mRNA) expression of TNF-alpha and IL-6 was measured by RT-PCR and the protein secretion of the two cytokines was determined by ELISA method. Western blot was used to analyze the activation of NF-kappaB in VSMC. RESULTS: IL-18 significantly increased the mRNA expression and protein secretion of TNF-alpha and IL-6 (P>0.01) in a dose-dependent and a time-dependent ways. NAC inhibited the mRNA expression and protein secretion of TNF-alpha and IL-6 induced by IL-18(P>0.01). Western blot results showed the NAC inhibited the IL-18-induced activation of NF-kappaB in VSMC. CONCLUSION: N-acetylcysteine antagonizes the production of TNF-alpha and IL-6 induced by IL-18 in VSMC.