Occupational exposure to diesel engine exhaust and serum cytokine levels

The International Agency for Research on Cancer has classified diesel engine exhaust (DEE) as a human lung carcinogen. Given that inflammation is suspected to be an important underlying mechanism of lung carcinogenesis, we evaluated the relationship between DEE exposure and the inflammatory response using data from a cross‐sectional molecular epidemiology study of 41 diesel engine testing workers and 46 unexposed controls. Repeated personal exposure measurements of PM_2.5 and other DEE constituents were taken for the diesel engine testing workers before blood collection. Serum levels of six inflammatory biomarkers including interleukin (IL)‐1, IL‐6, IL‐8, tumor necrosis factor (TNF)‐α, macrophage inflammatory protein (MIP)‐1β, and monocyte chemotactic protein (MCP)‐1 were analyzed in all subjects. Compared to unexposed controls, concentrations of MIP‐1β were significantly reduced by ～37% in DEE exposed workers (P < 0.001) and showed a strong decreasing trend with increasing PM_2.5 concentrations in all subjects (P_trend < 0.001) as well as in exposed subjects only (P_trend = 0.001). Levels of IL‐8 and MIP‐1β were significantly lower in workers in the highest exposure tertile of PM_2.5 (>397 µg/m³) compared to unexposed controls. Further, significant inverse exposure‐response relationships for IL‐8 and MCP‐1 were also found in relation to increasing PM_2.5 levels among the DEE exposed workers. Given that IL‐8, MIP‐1β, and MCP‐1 are chemokines that play important roles in recruitment of immunocompetent cells for immune defense and tumor cell clearance, the observed lower levels of these markers with increasing PM_2.5 exposure may provide insight into the mechanism by which DEE promotes lung cancer. Environ. Mol. Mutagen. 59:144–150, 2018. © 2017 Wiley Periodicals, Inc.     

Thirty autosomal insertion-deletion polymorphisms analyzed using the Investigator® DIPplex Kit in populations from Iraq,Lithuania, Slovenia,and Turkey

Thirty autosomal insertion-deletion (InDel) polymorphisms were analyzed in four populations from Iraq, Lithuania, Slovenia, and Turkey using the commercial kit Investigator® DIPplex. Genotyping issues were encountered for five of the 30 InDels. They were most probably caused by polymorphisms located in the primer binding sites. Population and forensic parameters were calculated. No significant deviations from Hardy-Weinberg equilibrium or significant linkage disequilibrium were detected. The observed heterozygosities ranged from 33% to 61% depending on the marker and the population. The combined probability of exclusion for the 30 markers was 99.7% in all four populations and the matching probabilities were 1 in 3–4 × 10¹² individuals. The multidimensional scaling plot drawn from F_ST distances showed a good concordance between the relative position of the 15 populations included in the plot and their geographic locations.     

Effects of atrazine on the proliferation and cytotoxicity of murine lymphocytes with the use of carboxyfluorescein succinimidyl ester-based flow cytometric approaches

Atrazine (ATZ) is one of the most commonly applied herbicides worldwide. ATZ has been associated with adverse effects on the immune system; however, the mechanism of its immunotoxicity has not been completely elucidated. In this study, the immunotoxic effects of ATZ on murine splenic lymphocytes and magnetic bead-enriched NK cells were investigated in vitro with the use of carboxyfluorescein succinimidyl ester (CFDA-SE)-based flow cytometric approaches. Proliferation responses, NK cell activity, and T-cell early activation were determined with CFDA-SE loading, CFDA-SE/propidium iodide (PI) staining, and CD69+ expression, respectively. Cell apoptosis/cycle, reactive oxygen species (ROS), and mitochondrial membrane potential (MMP) were evaluated using PI, 2′,7′-dichlorodihydrofluorescein diacetate, and rhodamine 123, respectively. The intracellular expressions of apoptosis-related Bcl-2 and caspase-3 were analyzed through intracellular staining and flow cytometry. Results showed that proliferation and NK cell activity were suppressed by ATZ treatment. Such suppression might be associated with the cell apoptosis induced by increased ROS and declined MMP. The underlying mechanism might be the induced caspase-3 expression and decreased Bcl-2 expression. ATZ could elicit immunotoxic effects on murine lymphocytes; its presence in the environment might compromise immune function in organisms. The flow cytometric methods presented in this study should be further investigated in immunotoxicology.     

HIV Infection,Sexual Behaviors,Sexual Networks,and Drug Use Among Rural Residents in Yunnan Province,China

This cross-sectional study examined HIV prevalence, sexual behaviors, sexual networks, and drug use among 591 participants from a rural community in Yunnan Province, China. Face-to-face interviews were conducted to collect information about sexual behavior, drug use, and sexual networks. Blood samples were collected and tested for HIV. Of the participants, 52.6% were male and 62.6% were Jingpo minority. The HIV prevalence was 5.5% overall and highest among the Jingpo minority (7.7%). Most participants were sexually experienced and 32.5% had had multiple sex partners. About 18.8% had used drugs, with the highest proportion among the Jingpo minority. HIV infection was independently correlated with drug use among males and with multiple sexual partnerships among females. A total of 336 independent sexual network components (mostly small, linear, and acyclic) were constructed. Eighty-percent were dyads involving two members and 20% involved three to 71 members. Coupled with the promotion of condom use, gender- and network-specific efforts are needed for HIV prevention targeting ethnic minorities in Yunnan.     

S1PR1 expression correlates with inflammatory responses to Newcastle disease virus infection

Newcastle disease virus (NDV) is the causative agent of Newcastle disease, which is characterized by inflammatory pathological changes in the organs of chickens. The inflammatory response to this disease has not been well characterized. Previous reports showed that the sphingosine-1-phosphate-1 receptor (S1PR1), a G protein-coupled receptor, is important to the activation of inflammatory responses. To understand better the viral pathogenesis and host inflammatory response, we analyzed S1PR1 expression during NDV infection. We observed a direct correlation between chicken embryo fibroblast (CEF) cellular inflammatory responses and S1PR1 expression. Virulent NDV-infected CEF cells also had elevated levels of pro-inflammatory cytokines (IL-1β, IL-6 and IL-18). When S1PR1 was inhibited by using the specific antagonist W146, pro-inflammatory cytokine production declined. Overexpression of S1PR1 resulted in increased virus-induced IL-1β production. S1PR1 expression levels did not impact significantly NDV replication. These findings highlight the important role of S1PR1 in inflammatory responses in NDV infection.     

Association of heart rate and diabetes among 0.5 million adults in the China Kadoorie biobank: Results from observational and Mendelian randomization analyses

Background and aimsObservational studies have associated resting heart rate with incident diabetes. Whether the associations are causal remains unclear. We aimed to examine the shape and strength of the associations and assessed the causal relevance of such associations in Chinese adults.Methods and resultsThe China Kadoorie Biobank enrolled 512,891 adults in China. Cox proportional hazard regression models was conducted to estimate hazard ratios (HRs) for the associations of resting heart rate with type 2 diabetes and total diabetes. Among 92,724 participants, 36 single-nucleotide polymorphisms (SNPs) related to resting heart rate were used to construct genetic risk score. We used Mendelian randomization analyses to make the causal inferences. During a median follow-up of 9 years, 7872 incident type 2 diabetes and 13,349 incident total diabetes were documented. After regression dilution bias adjustment, each 10 bpm higher heart rate was associated with about a 26% higher risk of type 2 diabetes (HR, 1.26 [95% CI, 1.23, 1.29]) and 23% higher risk of total diabetes (HR, 1.23 [95% CI, 1.20, 1.26]). Instrumental variable analyses showed participants at top quintile compared with those at bottom quintile had 30% higher risk for type 2 diabetes (HR, 1.30 [95% CI, 1.17, 1.43]), and 10% higher risk for total diabetes (HR, 1.10 [95% CI, 1.02, 1.20]).ConclusionsThis study provides evidence that resting heart rate is an important risk factor for diabetes risk. The results suggest that novel treatment approaches targeting reduction of high heart rate for incidence of diabetes may be worth further investigation.     

The effect of salt-water bath in the management of treatment-related peripheral neuropathy in cancer patients receiving taxane and platinum-based treatment

ObjectivesIn a clinical setting, patients have been observed to complain of discomfort and to discontinue treatment because of chemotherapy-induced peripheral neuropathy. This experimental study was conducted to determine the effect of a salt-water bath in the management of chemotherapy-induced peripheral neuropathy.MethodOne hundred and three patients who received taxane and platinum-based chemotherapy due to cancer and developed peripheral neuropathy associated with the treatment between December 2018 and June 2020 were included in the study. The patients were assigned to the control and experimental groups (1-warm salt-water and 2-cold salt-water) following the randomization checklist. While control groups did not receive any interventions, the patients in the salt-water group were asked to apply warm (41 °C) or cold-water (23–26 °C) baths to their hands/feet for 30 min every other day for 14 days. The data were collected at the beginning of the study and at the end of its first and second weeks using the Patient Information Form and National Cancer Institute (NCI)-CTCAE v5.0 toxicity criteria as well as the EORTC QLQ-C30 and EORTC QLQ-CIPN20 quality of life scales.ResultsThe patients had a mean age of 55.6 ± 10.3, and most of them were treated following a breast cancer diagnosis. At the beginning of the study, Grade 3 peripheral neuropathy severity and quality of life scores of the cold/warm salt-water and control groups were similar. Due to repeated follow-ups, it was determined that the peripheral neuropathy severity decreased and the quality of life scores increased statistically significantly in the patients in the cold salt-water bath group compared to the control group.ConclusionThis study's results suggest that a cold salt-water bath can be an effective approach in managing the development of peripheral neuropathy due to taxane and platinum-based treatment.