Appraising causal risk and protective factors for rheumatoid arthritis.

Aims: Mendelian randomization (MR) is considered to overcome the bias of observational studies, but there is no current meta-analysis of MR studies on rheumatoid arthritis (RA). The purpose of this study was to summarize the relationship between potential pathogenic factors and RA risk based on existing MR studies. Methods: PubMed, Web of Science, and Embase were searched for MR studies on influencing factors in relation to RA up to October 2022. Meta-analyses of MR studies assessing correlations between various potential pathogenic factors and RA were conducted. Random-effect and fixed-effect models were used to synthesize the odds ratios of various pathogenic factors and RA. The quality of the study was assessed using the Strengthening the Reporting of Observational Studies in Epidemiology using Mendelian Randomization (STROBE-MR) guidelines. Results: A total of 517 potentially relevant articles were screened, 35 studies were included in the systematic review, and 19 studies were eligible to be included in the meta-analysis. Pooled estimates of 19 included studies (causality between 15 different risk factors and RA) revealed that obesity, smoking, coffee intake, lower education attainment, and Graves' disease (GD) were related to the increased risk of RA. In contrast, the causality contribution from serum mineral levels (calcium, iron, copper, zinc, magnesium, selenium), alcohol intake, and chronic periodontitis to RA is not significant. Conclusion: Obesity, smoking, education attainment, and GD have real causal effects on the occurrence and development of RA. These results may provide insights into the genetic susceptibility and potential biological pathways of RA.

Tea Polysaccharide Prevents Colitis-Associated Carcinogenesis in Mice by Inhibiting the Proliferation and Invasion of Tumor Cells.

The imbalance between cell proliferation and apoptosis can lead to tumor progression, causing oncogenic transformation, abnormal cell proliferation and cell apoptosis suppression. Tea polysaccharide (TPS) is the major bioactive component in green tea, it has showed antioxidant, antitumor and anti-inflammatory bioactivities. In this study, the chemoprophylaxis effects of TPS on colitis-associated colon carcinogenesis, especially the cell apoptosis activation and inhibition effects on cell proliferation and invasion were analyzed. The azoxymethane/dextran sulfate sodium (AOM/DSS) was used to induce the colorectal carcinogenesis in mice. Results showed that the tumor incidence was reduced in TPS-treated AOM/DSS mice compared to AOM/DSS mice. TUNEL staining and Ki-67 immunohistochemistry staining showed that the TPS treatment increased significantly the cell apoptosis and decreased cell proliferation among AOM/DSS mice. Furthermore, TPS reduced the expression levels of the cell cycle protein cyclin D1, matrix metalloproteinase (MMP)-2, and MMP-9. In addition, in vitro studies showed that TPS, suppressed the proliferation and invasion of the mouse colon cancer cells. Overall, our findings demonstrated that TPS could be a potential agent in the treatment and/or prevention of colon tumor, which promoted the apoptosis and suppressed the proliferation and invasion of the mouse colon cancer cells via arresting cell cycle progression.

[Association between telomere length and occupational polycyclic aromatic hydrocarbons exposure].

OBJECTIVE: To explore the association between polycyclic aromatic hydrocarbons (PAHs) exposure and telomere length (TL), so as to investigate the effective biomarkers to evaluate the genetic damage in peripheral blood of workers exposed to PAHs. METHODS: The exposure group consisted of 145 coke-oven workers (including 30 top-oven workers, 76 side-oven workers and 39 bottom-oven workers), and the non-exposure control group comprised 68 medical staffs. At 6 hours after the weekend duty shift, the samples of urine and 1 ml venous blood were collected from each subject. Airborne benzene-soluble matter (BSM) and particulate-phase B(a)P in the working environment of coke-oven and controls were sampled and analyzed. The concentration of urinary 1-hydroxypyrene (1-OHPyr) was determined. A real-time PCR method was used to determine the relative telomere length (RTL) of genomic DNA in peripheral blood. The relationship between the RTL and external exposure of PAHs, the potential factors which might have influence on TL were analyzed. RESULTS: The medians of air BSM and particulate-phase B(a)P were higher in coke-oven (BSM: 328.6 µg/m(3); B(a)P: 926.9 ng/m(3)) than those in control working environment (BSM:97.8 µg/m(3); B(a)P: 49.1 ng/m(3)). The level of 1-OHPyr among coke-oven workers was significantly higher than that of non-exposed group (12.2 µmol/mol Cr vs 0.7 µmol/mol Cr; t = 26.971, P < 0.01). RTL in coke-oven workers were significantly shorter than those of controls (1.10 ± 0.75 vs 1.43 ± 1.06; t = 2.263, P = 0.026), and after adjusting for cigarettes per day and urinary 1-OHPyr, the significant difference was still observed (F(adju) = 5.496, P(adju) = 0.020). Stratification analysis found that RTL among the male and non-drinking groups in coke-oven workers were shorter than those the same sex and alcohol using status in controls (1.08 ± 0.73 vs 1.51 ± 1.10, F = 9.212, P = 0.003; 0.96 ± 0.38 vs 1.26 ± 0.46, F = 6.484, P = 0.012). Significant correlation between RTL and age was found (r = -0.284, P = 0.019) in non-exposure group. CONCLUSION: PAH-exposure has effect on TL of genomic DNA in peripheral blood, which is mainly observed in the male and non-drinking groups between PAH-exposed workers and controls. It indicates that TL of genomic DNA in peripheral blood might be an effective biomarker as PAH-induced genetic damage.

[Mutagen sensitivity in peripheral blood lymphocytes among coke-oven workers].

OBJECTIVE: To investigate the sensitivity to bleomycin (BLM) in peripheral blood lymphocytes (PBL) among coke-oven workers. METHODS: Ninty-four coke-oven workers with exposure to a high level of polycyclic aromatic hydrocarbons and 64 non-coke-oven workers (control) were recruited into this study. PBL was challenged by 8 microg/ml BLM, a known carcinogen, to induce certain amount of DNA damage, the difference of olive tail moment (TM) measured by comet assay before and after BLM treatment reflected the sensitivity towards mutagens. RESULTS: The distribution of age, sex, and prevalence of smoking and drinking were not significantly different between these two groups. The geometric mean of urinary 1-hydroxypyrene (1-OHP) was significantly higher in coke-oven workers than in controls (9.0 versus 1.5 microg/L, t = -9.317, P < 0.01). The coke-oven workers showed significantly higher sensitivity to BLM than controls (17.7 versus 14.9, t = -2.583, P = 0.01). A large inter-group difference in sensitivity to BLM was observed in both controls and coke-oven workers. Stratification analysis revealed the significant association between high 1-OHP level (> 9.0 microg/L) and increased sensitivity to BLM (F = 4.001, P = 0.05) among coke-oven workers. Smoking subjects showed a significant higher value of sensitivity than nonsmokers in controls but not in coke-oven workers. No significant difference was observed between age, drinking status, coking history or external exposure class and BLM sensitivity. CONCLUSION: Exposure to coke oven emission could increase the sensitivity to mutagens, which might be a reason of high incidence of lung cancer among coke-oven workers.

Enhancement of DNA vaccine-induced immune responses by a 72-bp element from SV40 enhancer.

BACKGROUND: Although DNA vaccine is considered as the next generation of vaccine, most DNA vaccine candidates are still suffering from the relatively weak immunogenicity despite the increased dosage of plasmid DNA administered. In order to enhance the immune responses elicited by a codon-optimized HIV gag DNA vaccine, a modified plasmid vector pDRVI1.0 and a booster immunization with replicating Tiantan vaccinia (RTV) strain expressing the same gene were employed. METHODS: Vector pDRVI1.0 was constructed through inserting the 72-bp element from the SV40 enhancer, which was reported promoting nuclear transport of plasmid DNA, to the upstream of cytomegalovirus enhancer/promoter region of the plasmid vector pVR1012. Gene expression levels from expression plasmids based on pDRVI1.0 and pVR1012 were tested. Humoral and cellular immune responses induced by DNA vaccine alone or DNA prime-RTV boost regimen were determined in mice. RESULTS: It was shown that the 72-bp element significantly enhanced the gene expression level in non-dividing cells. gag-specific humoral and cellular immune responses induced by DNA vaccination were both significantly improved, while the Th1/Th2 balance was not obviously affected by the 72-bp element. RTV boosting further significantly enhanced DNA vaccine-primed antibody and T cell responses in a Th1-biased manner. CONCLUSIONS: The 72-bp SV40 enhancer element should be included in the DNA vaccine vector and RTV strain is a very efficient live vector for boosting immunization.