Exposure to heavy metal elements may significantly increase serum prostate-specific antigen levels with overdosed dietary zinc.

BACKGROUND: Serum prostate-specific antigen (PSA) is a primary metric for diagnosis and prognosis of prostate cancer (PCa). Exposure to heavy metals, such as lead, cadmium, mercury, and zinc can impact PSA levels in PCa patients. However, it is unclear whether this effect also occurs in men without PCa, which may lead to the overdiagnosis of PCa. METHOD: Data on a total of 5089 American men who had never been diagnosed with PCa were obtained from the National Health and Nutrition Examination Survey performed from 2003-2010. The relationship between serum PSA levels (dependent variable) and concentrations of lead (µmol/L), cadmium (nmol/L), and mercury (µmol/L) were investigated with dietary zinc intake being used as a potential modifier or covariate in a weighted linear regression model and a generalized additive model. A series of bootstrapping analyses were performed to evaluate sensitivity and specificity using these models. RESULTS: Regression analyses suggested that, in general, lead, cadmium, or mercury did not show an association with PSA levels, which was consistent with the results of the bootstrapping analyses. However, in a subgroup of participants with a high level of dietary zinc intake (≥14.12 mg/day), a significant positive association between cadmium and serum PSA was identified (1.06, 95% CI, P = 0.0268, P for interaction=0.0249). CONCLUSIONS: With high-level zinc intake, serum PSA levels may rise in PCa-free men as the exposure to cadmium increases, leading to a potential risk of an overdiagnosis of PCa and unnecessary treatment. Therefore, environmental variables should be factored in the current diagnostic model for PCa that is solely based on PSA measurements. Different criteria for PSA screening are necessary based on geographical variables. Further investigations are needed to uncover the biological and biochemical relationship between zinc, cadmium, and serum PSA levels to more precisely diagnose PCa.

Chemical composition and adjuvant properties of the macromolecules from cultivated Cistanche deserticola Y. C. Ma as an immunopotentiator.

The study aims to investigate the constituents, adjuvant effects, and underlying mechanisms of purified polysaccharides from cultivated Cistanche deserticola (C. deserticola). Two macromolecules designated as CCDP-1 (26.5 kDa) and CCDP-2 (32.3 kDa) from C. deserticola were respectively identified as carbohydrate-lignin complexes with 44.1 % and 43.8 % lignin. CCDP-1 and CCDP-2 were composed of glucose, rhamnose, galactose, arabinose, and mannose respectively in the molar ratios of 7.22: 5.98:2.51:1.81:1.00 and 6.57:8.48:4.20:2.72:1.00. An in vitro experiment revealed that endotoxin-free CCDP-1 and CCDP-2 promoted splenocyte proliferation without cytotoxicity, but CCDP-2 induced dendritic cell (DC) maturation more efficiently than CCDP-1. An in vivo experiment suggested that CCDP-2 enhanced OVA-specific antibody production, antigen-specific T-cell activation, IFN-γ production, IL-4 production, and DC activation. Notably, CCDP-2 elicited a Th1-biased response. Mechanically, CCDP-2 upregulated CD40, CD80, CD86, and MHC II, facilitated allogeneic T-cell proliferation and Th1/Th2 cytokines, improved IFN-γ, IL-12, IL-6, and TNF-α production, and decreased endocytosis from DCs in vitro. Blocking assays indicated that TLR2 and TLR4 were the membrane receptor candidates of DCs. Western blot implied that CCDP-2 with the immune-enhancing activities were involved in the activation of MAPKs and NF-κB pathways in a dose-/time-related manner and could be employed as a more balanced Th1/Th2 adjuvant for vaccine exploitation.

Efficacy and Safety of Opioids in Treating Cancer-Related Dyspnea: A Systematic Review and Meta-Analysis Based on Randomized Controlled Trials.

BACKGROUND: Dyspnea is one of the most distressing symptoms encountered by advanced cancer patients. In this study, we aimed to evaluate the role of opioids in the management of cancer-related dyspnea. METHODS: A systematic review and meta-analysis based on Randomized Controlled Trials was conducted in the databases PUBMED, EMBASE, and Cochrane Central Register of Controlled Trials testing the effect of opioids in relieving cancer-related dyspnea. Subgroup and sensitivity analyses were performed to evaluate various types of opioids in dyspnea management and stabilization of the study respectively. RESULTS: Eleven RCTs fulfilled the eligibility criteria and had a total of 290 participants. Nine of these studies were included in meta-analyses. Compared with control, opioid therapy showed a small positive effect in dyspnea, SMD-0.82 (95%CI = -1.54 to -0.10) and Borg score, WMD-0.95 (95%CI = -1.83 to -0.06); Opioid therapy did not increase the risk of somnolence, OR0.93 (95%CI = 0.34 to 2.58), whereas a negative effect on respiratory rate was observed,WMD-1.89 (95%CI = -3.36 to -0.43); Also, there was no evidence to suggest improved performance of the 6MWT test, WMD6.49 (95%CI = -34.23 to 47.21), or the level of peripheral oxygen saturation, WMD0.33 (95%CI = -0.59 to 1.24) after opioid therapy. Subgroup analysis yielded a small positive effect for morphine on dyspnea, SMD-0.78 (95%CI = -1.45 to -0.10), whereas fentanyl showed no improvement in dyspnea, SMD-0.44 (95%CI = -0.89 to 0.02). Sensitivity analysis showed no changes in the direction of effect when any one study was excluded from the meta-analyses. CONCLUSIONS: Our systematic review and meta-analysis indicated low quality evidence for a small positive effect of opioids in cancer-related dyspnea. Evidence for safety is insufficient as comprehensive adverse events were not adequately reported in studies.

MicroRNA miR-214 Inhibits Snakehead Vesiculovirus Replication by Promoting IFN-α Expression via Targeting Host Adenosine 5'-Monophosphate-Activated Protein Kinase.

BACKGROUND: Snakehead vesiculovirus (SHVV), a new rhabdovirus isolated from diseased hybrid snakehead, has emerged as an important pathogen during the past few years in China with great economical losses in snakehead fish cultures. However, little is known about the mechanism of its pathogenicity. MicroRNAs are small noncoding RNAs that posttranscriptionally modulate gene expression and have been indicated to regulate almost all cellular processes. Our previous study has revealed that miR-214 was downregulated upon SHVV infection. RESULTS: The overexpression of miR-214 in striped snakehead (SSN-1) cells inhibited SHVV replication and promoted IFN-α expression, while miR-214 inhibitor facilitated SHVV replication and reduced IFN-α expression. These findings suggested that miR-214 negatively regulated SHVV replication probably through positively regulating IFN-α expression. Further investigation revealed that adenosine 5'-monophosphate-activated protein kinase (AMPK) was a target gene of miR-214. Knockdown of AMPK by siRNA inhibited SHVV replication and promoted IFN-α expression, suggesting that cellular AMPK positively regulated SHVV replication and negatively regulated IFN-α expression. Moreover, we found that siAMPK-mediated inhibition of SHVV replication could be partially restored by miR-214 inhibitor, indicating that miR-214 inhibited SHVV replication at least partially via targeting AMPK. CONCLUSION: The findings of this study complemented our early study, and provide insights for the mechanism of SHVV pathogenicity. SHVV infection downregulated miR-214, and in turn, the downregulated miR-214 increased the expression of its target gene AMPK, which promoted SHVV replication via reducing IFN-α expression. It can therefore assume that cellular circumstance with low level of miR-214 is beneficial for SHVV replication and that SHVV evades host antiviral innate immunity through decreasing IFN-α expression via regulating cellular miR-214 expression.

Association between Th17-related cytokines and risk of non-small cell lung cancer among patients with or without chronic obstructive pulmonary disease.

BACKGROUND: CD4 (+) T helper 17 (Th17) cells play critical roles in inflammation and tumor development. The involvement of Th17 cells in chronic obstructive pulmonary disease (COPD)-type inflammation-associated lung cancer has also been confirmed in animal models. However, to the authors' knowledge, it is unknown whether the role of Th17 cells is different in patients with lung cancer complicated with COPD compared with those without COPD. In the current study, the authors attempted to determine the association between the circulating levels of Th17-related cytokines and the clinical characteristics of non-small cell lung cancer (NSCLC) in patients with or without COPD. METHODS: The authors designed a matched case-control study that included 70 patients with NSCLC with COPD, 148 patients with NSCLC without COPD, and 148 healthy controls. The data regarding the clinicopathological features of these participants were collected. Circulating levels of Th17-related cytokines, including interleukin (IL) 23 (IL-23), IL-17A, IL-17F, IL-22, and tumor necrosis factor-α, were measured. RESULTS: The circulating levels of IL-23, IL-17A, IL-17F, IL-22, and tumor necrosis factor-α were found to be significantly higher in the patients with NSCLC compared with the healthy controls (P<.05). The elevated levels were found to be significantly associated with lung cancer risk (P<.05). However, no significant differences were found between patients with NSCLC with COPD and patients without COPD. It is interesting to note that, among patients with NSCLC without COPD, the levels of these cytokines were consistently higher among patients with stage I to stage IIIA disease compared with those with stage IIIB to stage IV disease (P<.05). In addition, the 5 Th17-related cytokines demonstrated pairwise correlations, with Spearman rank correlation coefficients of 0.646 to 0.888 (P<.05). CONCLUSIONS: The results of the current study indicate a clear association between the Th17-related cytokine profile and the risk of NSCLC complicated by the presence or absence of COPD.