Relationship between food-derived antioxidant vitamin intake and breast cancer risk: a mendelian randomized study.

BACKGROUND: In previous observational studies, food-derived antioxidant vitamins have been suggested to be associated with breast cancer. However, the findings were inconsistent and the causal relationship could not be clearly elucidated. To confirm the potential causal relationship between food-derived antioxidants (retinol, carotene, vitamin C and vitamin E) and the risk of breast cancer, we conducted a two-sample Mendelian randomization (MR) study. METHODS: The instrumental variables (IVs) as proxies of genetic liability to food-derived antioxidant vitamins were obtained from the UK Biobank Database. We extracted breast cancer data (122,977 cases and 105,974 controls) from the Breast Cancer Consortium (BCAC). In addition, we studied estrogen expression status categorically, including estrogen receptor positive (ER+) breast cancer (69,501 cases and 105,974 controls) and versus estrogen receptor (ER-) negative breast cancer (21,468 cases and 105,974 controls). We performed two-sample Mendelian randomization study, and inverse variance-weighted (IVW) test was regarded as main analysis. Sensitivity analyses were further conducted to assess heterogeneity and horizontal pleiotropy. RESULTS: The results of IVW showed that among the four food-derived antioxidants, only vitamin E had protective effect on the risk of overall breast cancer (OR = 0.837, 95% CI 0.757-0.926, P = 0.001) and ER+ breast cancer (OR = 0.823, 95% CI 0.693-0.977, P = 0.026). However, we found no association between food-derived vitamin E and ER- breast cancer. CONCLUSIONS: Our study suggested food-derived vitamin E can decrease the risk of breast cancer overall and ER+ breast cancer, and the robustness of our results was confirmed by sensitivity analyses.

The association between circulating docosahexaenoic acid and lung cancer: A Mendelian randomization study.

BACKGROUND: Lung cancer is a malignant tumor with a high incidence, it is vital to identify modifiable and avoidable risk factors for primary prevention, which can significantly lower the risk of cancer by preventing exposure to hazards and altering risky behavior. Some observational studies suggest that an increase in docosahexaenoic acid (DHA) consumption can reduce lung cancer risk. However, interpretation of these observational findings is difficult due to residual confounding or reverse causality. To evaluate the link between DHA and lung cancer, we have undertaken this analysis to examine the causal association between DHA and the risk of lung cancer using a two-sample Mendelian randomization (MR) framework. METHODS: We performed a two-sample MR analysis to evaluate the causal effect of plasma DHA levels on lung cancer risk. For the exposure data, we extracted genetic variants as instrumental variables (IVs) that are strongly associated with DHA from a large-scale genome-wide association study (GWAS). We obtained the corresponding effect estimates for IVs on the risk of lung cancer with 11,348 cases and 15,861 controls. Finally, we applied Mendelian randomization analysis to obtain preliminary MR results and performed sensitivity analyses to verify the robustness of our results. RESULTS: According to the primary MR estimates and further sensitivity analyses, a higher serum DHA level was associated with a higher risk of lung cancer [OR = 1.159, 95% CI (1.04-1.30), P = 0.01]. For lung adenocarcinoma, the results also showed a close correlation between the DHA level and lung adenocarcinoma [OR = 1.277, 95% CI (1.09-1.50), P = 0.003], but it was not statistically significant for squamous cell carcinoma [OR = 1.071, 95% CI (0.89-1.29), P = 0.467]. CONCLUSIONS: Our study revealed that plasma DHA is positively associated with the risk of lung cancer overall, especially for lung adenocarcinoma. This study provides new information to develop dietary guidelines for primary lung cancer prevention.

Causal associations between dietary antioxidant vitamin intake and lung cancer: A Mendelian randomization study.

Background: Oxidative stress is currently considered to be closely related to the occurrence of respiratory tumors, especially lung cancer. Many observational studies have shown that increased antioxidant intake can reduce the risk of lung cancer, but the results are still controversial. Therefore, we performed a two-sample Mendelian randomized (MR) analysis to clarify the causal relationship between antioxidant vitamins and lung cancer. Methods: To assess the causal effect of dietary antioxidant vitamin intake on lung cancer, we conducted a two-sample MR analysis and we extracted single-nucleotide polymorphisms (SNPs) that are associated with antioxidants from genome-wide association studies (GWASs) of the UK biobank. We gathered summary data for lung cancer from the International Lung Cancer Consortium (ILCCO), including 11,348 cases and 15,861 controls, and applied the inverse-variance weighted (IVW) method as the primary MR analysis, and performed a sensitivity analysis to verify the results. Results: The results showed that higher dietary retinol intake was causally associated with lung cancer overall [odds ratio (OR) = 1.844, 95% CI, 1.359-2.502, p = 0.00009], squamous cell lung cancer (OR = 2.162, 95% CI, 1.117-4.183, p = 0.022), and lung adenocarcinoma (OR = 1.706, 95% CI, 1.084-2.685, p = 0.021). Additionally, carotene was positively correlated with lung adenocarcinoma (OR = 1.510, 95% CI, 1.002-2.276, p = 0.049). However, there was a non-significant relationship between the intake of other dietary antioxidants (vitamin C and vitamin E) and lung cancer. Conclusion: Our research showed that dietary retinol intake has an adverse impact on lung cancer, and carotene might increase the risk of adenocarcinoma. This highlights the importance of revealing the underlying mechanisms of dietary antioxidant vitamins in lung cancer and delivers an important health message that dietary antioxidant vitamin intake may not be necessary for the prevention of lung cancer. It also provides a basis for future research.

Seroprevalence and Risk Factors of Toxoplasma gondii Infection Among High-Risk Populations in Jiangsu Province, Eastern China.

Toxoplasma gondii, an opportunistic protozoan, infects one-third of people worldwide and could lead to serious outcomes in immunodeficient or immunocompromised populations. The present study aimed to investigate the prevalence and risk factors for T. gondii infection among high-risk populations in Jiangsu Province, eastern China. We conducted a cross-sectional survey among 4 categories of populations in 13 prefectures including HIV/AIDS patients, livestock breeding/processing (B/P) staff, pregnant women, and cancer patients. We detected specific immunoglobulin G and M (IgG and IgM) levels for each participant using enzyme-linked immunosorbent assay (ELISA) and asked to complete a questionnaire for each participant that covered sociodemographic information as well as the basic knowledge of attitudes toward and the practices for the prevention of toxoplasmosis. A total of 5231 participants distributed across 13 prefecture-level cities was surveyed, including 2455 males and 2776 females. Total seropositivity rate in each population category was as follows: 9.08% (HIV/AIDS patients), 11.65% (livestock B/P staff), 5.50% (pregnant women), and 12.89% (cancer patients). We detected IgM positivity in HIV/AIDS patients (0.47%, 6/1289), livestock B/P staff (0.08%, 1/1330), and cancer patients (0.46%, 6/1303) but not in pregnant women. Further, we detected IgM+IgG positivity only in cancer patients (0.31%, 4/1303). The seropositivity rate for pregnant women was significantly lower, while cancer patients were significantly higher. Higher educational levels were associated with lower seropositivity rates for T. gondii infection. High seropositivity rates were associated with long period of HIV infection among HIV/AIDS patients, frequent contact with livestock among livestock breeding/processing staff and male older patients among cancer patients, respectively. Analysis of practices across all participants showed that frequent contact with pets in everyday life or using the same cutting board for both raw and cooked foods leads to higher seropositivity rates. Therefore, we obtained the seroprevalence and risk factors of toxoplasmosis among high-risk populations in Jiangsu Province which could provide evidence for the implementation of control measures in the near future.

Prevalence of intestinal helminth infections in Jiangsu Province, eastern China; a cross-sectional survey conducted in 2015.

BACKGROUND: Intestinal helminth infections are a serious public health problem in developing countries. Jiangsu, an eastern coastal province of China, has an environment conducive to the transmission of intestinal parasites, and suffered human infection rates of 71.75% in 1990. Due to comprehensive anti-transmission measures undertaken throughout the province in the 1990s, the prevalence had decreased to 9.28% in 2002. In order to assess the current epidemic situation for intestinal parasitic infections in Jiangsu province, a province-wide cross-sectional survey was carried out in 2015. METHODS: Surveys were conducted in two main settings; rural (for soil-transmitted parasites) and urban (for Clonorchis sinensis), selected through stratified random sampling. Human infection rates were evaluated through the detection of helminth eggs or cysts (oocysts or trophozoites) of intestinal protozoa in fecal samples by microscopy. Secondary intermediate and reservoir hosts were surveyed for C. sinensis infection. Questionnaires were completed by each participant to evaluate knowledge, attitude and practice of soil-transmitted parasite and C. sinensis avoidance. RESULTS: 115 out of 30153 participants (0.38%) had intestinal helminths or protozoa. There were eight species of helminth detected and the most common parasite was the hookworm Ancylostoma duodenale. In rural settings, there were significant differences in infection rates between participants of differing economic status. In urban settings, only four cases of C. sinensis infection were detected. However, secondary intermediate and reservoir hosts were found to harbor parasites. The questionnaire survey revealed that 38.42% participants were not aware of how humans become infected by hookworms. Knowledge and awareness of C. sinensis was similarly low, with 53.22% participants combining the use of chopping boards for raw and cooked food items when preparing meals. CONCLUSIONS: The prevalence of intestinal parasitic infections in Jiangsu Province in eastern China has decreased from 71.57% in 1990 to 0.38% in 2015. Control measures should now focus on parasitic infections in the elderly and in children, health promotion and the development of alternative detection methods.

Effects of Chinese Medicine as Adjunct Medication for Adjuvant Chemotherapy Treatments of Non-Small Cell Lung Cancer Patients.

The aim was to evaluate the effects of traditional Chinese medicine (TCM) as a combination medication with adjuvant chemotherapy on postoperative early stage non-small cell lung cancer (NSCLC) patients. The 314 patients with completely resected stage IB, II or IIIA cancers were assigned into vinorelbine plus cisplatin/carboplatin (NP/NC) (control, n = 158) and NP/NC with additional TCM (intervention, n = 156) groups. The primary endpoint was QOL scores; secondary endpoints were the toxicity and safety of the regimens. The NP/NC regimen caused mild (grade 1 or 2) non-hematologic toxic effects in the patients comprising vomiting (43.6%), fatigue (36.9%), pain (23%), dry mouth (27.6%) and diarrhea (7.9%). The incidence of adverse events was significantly lower in the intervention group than in the control group (0.57% vs 4.02%, P = 0.037). Transient severe (grade 3 or 4) hematological toxic effects occurred less often (hemoglobin reduction (11.9 vs 22.5 percent) and total bilirubin increased (to 42.1 vs 46.2%) in the intervention compared to the control group during the 2nd chemotherapy cycle. When combined with adjuvant chemotherapy, TCM led to partial relief of symptoms in addition to a reduction of side-effects and adverse events caused by the NP/NC regimens.

Evaluation of protective efficacy induced by different heterologous prime-boost strategies encoding triosephosphate isomerase against Schistosoma japonicum in mice.

BACKGROUND: In China, schistosomiasis japonica is a predominant zoonotic disease, and animal reservoir hosts in the environment largely sustain infections. The development of transmission-blocking veterinary vaccines is urgently needed for the prevention and efficient control of schistosomiasis. Heterologous prime-boost strategy is more effective than traditional vaccination and homologous prime-boost strategies against multiple pathogens infection. In the present study, to further improve protective efficacy, we immunized mice with three types of heterologous prime-boost combinations based on our previously constructed vaccines that encode triosphate isomerase of Schistosoma japonicum, tested the specific immune responses, and evaluated the protective efficacy through challenge infection in mice. METHODS: DNA vaccine (pcDNA3.1-SjTPI.opt), adenoviral vectored vaccine (rAdV-SjTPI.opt), and recombinant protein vaccine (rSjTPI) were prepared and three types of heterologous prime-boost combinations, including DNA i.m. priming-rAdV i.m. boosting, rAdV i.m. priming-rAdV s.c. boosting, and rAdV i.m. priming-rSjTPI boosting strategies, were carried out. The specific immune responses and protective efficacies were evaluated in BALB/c mice RESULTS: Results show that different immune profiles and various levels of protective efficacy were elicited by using different heterologous prime-boost combinations. A synergistic effect was observed using the DNA i.m. priming-rAdV i.m. boosting strategy; however, its protective efficacy was similar to that of rAdV i.m. immunization. Conversely, an antagonistic effect was generated by using the rAd i.m. priming-s.c. boosting strategy. However, the strategy, with rAdV i.m. priming- rSjTPI s.c. boosting, generated the most optimal protective efficacy and worm or egg reduction rate reaching up to 70% in a mouse model. CONCLUSIONS: A suitable immunization strategy, rAdV i.m. priming-rSjTPI boosting strategy, was developed, which elicits a high level of protective efficacy against Schistosoma japonicum infection in mice.

iTRAQ analysis of low-phytate mung bean sprouts treated with sodium citrate, sodium acetate and sodium tartrate.

The effects of sodium citrate (SC), sodium acetate (SA) and sodium tartrate (ST) spraying on mung bean germination were investigated. Exogenous SC, ST and SA treatments significantly reduced the phytic acid content and increased the antioxidant enzyme activities. In this study, an iTRAQ-based proteomic approach was employed to explore the proteomes of mung bean sprouts, and 81, 101 and 90 differentially expressed proteins were identified in 4-day-old SC-, SA- and ST-treated mung bean sprouts, with 38 proteins present in all samples. Functional classification analysis showed that most of the differentially expressed proteins in mung bean sprouts subjected to the three treatments were involved in carbohydrate and energy metabolism. The inhibitory effect of the SA treatment was probably due to impairments in protein biosynthesis, whereas enhanced energy metabolism, accelerated reserve hydrolysis and protein processing were very important strategies for growth stimulation in response to ST and SC treatments.

Enhancement of protective efficacy through adenoviral vectored vaccine priming and protein boosting strategy encoding triosephosphate isomerase (SjTPI) against Schistosoma japonicum in mice.

BACKGROUND: Schistosomiasis japonica is a zoonotic parasitic disease; developing transmission blocking veterinary vaccines are urgently needed for the prevention and control of schistosomiasis in China. Heterologous prime-boost strategy, a novel vaccination approach, is more effective in enhancing vaccine efficacy against multiple pathogens. In the present study, we established a novel heterologous prime-boost vaccination strategy, the rAdV-SjTPI.opt intramuscular priming and rSjTPI subcutaneous boosting strategy, and evaluated its protective efficacy against Schistosoma japonicum in mice. METHODOLOGY/PRINCIPAL FINDINGS: Adenoviral vectored vaccine (rAdV-SjTPI.opt) and recombinant protein vaccine (rSjTPI) were prepared and used in different combinations as vaccines in a mouse model. The specific immune responses and protective efficacies were evaluated. Furthermore, the longevity of protective efficacy was also determined. Results showed that the rAdV-SjTPI.opt priming-rSjTPI boosting strategy elicited higher levels of specific IgG responses and broad-spectrum specific cellular immune responses. The protective efficacy could reach up to nearly 70% and 50% of protection could be observed at 10 weeks after the last immunization in mice. CONCLUSIONS/SIGNIFICANCE: The rAdV-SjTPI.opt intramuscular priming-rSjTPI subcutaneous boosting vaccination strategy is a novel, highly efficient, and stable approach to developing vaccines against Schistosoma japonicum infections in China.

[Surveillance of echinococcosis in Liyang City from 2008 to 2012].

OBJECTIVE: To investigate the Echinococcus infection of people and domestic animals in Liyang City, so as to provide the evidence for the establishment of control measures of echinococcosis. METHODS: The formerly confirmed cases and clue cases were investigated. The Echinococcus antibody in serum of children aged from 7 to 12 years old and adults in key towns and control towns was detected with ELISA, and the antigen in fecal samples of dogs in key towns was also detected. B ultrasound was applied to examine the ELISA positive cases, family member and the neighbored people around them. The sheep in the market were dissected and examined for Echinococcus. RESULTS: The Echinococcus antibody positive rates were 0.93% and 0.52% in children and adults, respectively. The Echinococcus antigen positive rate was 0.95% in dogs. There were no significant difference between the positive rates of the children and adults (CHI2 = 2.124, P > 0.05). No cases were found by ultrasonic examination and no Echinococcus infection was found in the sheep. CONCLUSION: The people with Echinococcus antibody in serum and dogs with antigen in their feces are found in the surveillance of echinococcosis, therefore, there exists the complete chain of transmission in local. Thus, in the prevention and control work for the disease, the monitoring of dog feces, quarantine of sheep from other regions, as well as the population health education in key areas should be strengthened.

Functional identification of the DNA packaging terminase from Pseudomonas aeruginosa phage PaP3.

Terminase proteins are responsible for DNA recognition and initiation of DNA packaging in phages. We previously reported the genomic sequence of a temperate Pseudomonas aeruginosa phage, PaP3, and determined its precise integration site in the host bacterial chromosome. In this study, we present a detailed functional identification of the DNA packaging terminase for phage PaP3. The purified large subunit p03 was demonstrated to possess ATPase and nuclease activities, as well as the ability to bind to specific DNA when it is unassembled. In addition, a small terminase subunit (p01) of a new type was found and shown to bind specifically to cos-containing DNA and stimulate the cos-cleavage and ATPase activities of p03. The results presented here suggest that PaP3 utilizes a typical cos site mechanism for DNA packaging and provide a first step towards understanding the molecular mechanism of the PaP3 DNA packaging reaction.

[Epidemiological survey of echinococcosis in some areas of Jiangsu Province].

OBJECTIVE: To understand the prevalence of echinococcosis in some areas of Jiangsu Province, so as to provide the evidence for making practical control measures. METHODS: The cases were determined by a retrospective survey and case-clues survey. All canine feces were tested by immunological fecal antigen in the villages of the local infection suspected cases. The antigen-positive feces were detected for E. chinococcus eggs by Kato-Katz technique. A serological investigation was administrated to search infected persons by double methods of enzyme-labeled immune assay and point immuno-gold filtration assay in the focus groups around the local infection suspected cases, and some students aged from seven to twelve years in their townships and in five different-orientation townships sampled randomly in their counties. The antibody-positive people were confirmed further by using imaging detection. RESULTS: There were 10 imported cases and 16 local infection suspected cases. Twenty canine feces were positive among 1 938 samples, and the positive rate was 1.03%. However, no pathogen was found. Of 12 473 serum samples, 72 were positive in sera immunological antibody test (0.58%), but no cystic nodules were found by imaging detection. CONCLUSION: There is no direct evidence for confirming the presence of infectious source and foci of echinococcosis in Jiangsu Province. However, the surveillance of echinococcosis is still needed.

[Cloning, expression and evaluation on effect in serological diagnosis of cysteine protease of Clonorchis sinensis].

OBJECTIVE: To clone and express the cysteine protease of Clonorchis sinensis and evaluate its effect on immunodiagnosis of human clonorchiasis. METHODS: Based on a cysteine protease gene fragment of C. sinensis (CS-CP, GenBank accession: AF093242), a pair of primers were designed and amplified from total cDNA of C. sinensis, and the gene was cloned into plasmid pPIC9K and expressed in Pichia pastoris GS115. The expressed product was purified. Ten BALA/c mice were immunized with the purified CS-CP, and the anti CS-CP antibody in the sera of immunized mice was tested with ELISA. Finally, its effect on serodiagnosis was evaluated with Dot-ELISA and Western blot. RESULTS: The CS-CP gene (approximately 927 bp) was successfully amplified, cloned and expressed in Pichia pastoris GS115. The sera of mice immunized with purified rCS-CP could be recognized by the soluble antigen of C. sinensis adult worms and its special anti CS-CP antibody titer was high (1: 64 000). The rCS-CP was probed by Dot-ELISA and Western-blot with sera from patients with clonorchiasis and other parasitic infections, and it had a sensitivity of 91.7% (55/60) in diagnosis of clonorchiasis and a specifity of 97.6% (82/84) for healthy population. The rCS-CP had no cross-reaction with the patients of schistosomiasis japonica, but had a cross-reactivity of 20.0% (2/10) with the patients with paragonimiasis westermani. CONCLUSIONS: rCS-CP possesses a favorable diagnostic effect and it is a better serodiagnostic one among recombinant antigens.

Identification of lytic bacteriophage MmP1, assigned to a new member of T7-like phages infecting Morganella morganii.

MmP1 (Morganella morganii phage 1) is a lytic bacteriophage newly isolated from the host bacterium M. morganii. The entire genome was sequenced, and final assembly yielded a 38,234bp linear double-stranded DNA (dsDNA) with a G+C content of 46.5%. In the MmP1 genome, 49 putative genes, 10 putative promoters and 2 predicted sigma-independent terminators were determined through bioinformatic analysis. A striking feature of the MmP1 genome is its high degree of similarity to the T7 group of phages. All of the 49 predicted genes exist on the same DNA strand, and functions were assigned to 35 genes based on the similarity of the homologues deposited in GenBank, which share 30-80% identity to their counterparts in T7-like phages. The analyses of MmP1 using CoreGenes, phylogenetic tree of RNA polymerase and structural proteins have demonstrated that bacteriophage MmP1 should be assigned as a new member of T7-like phages but as a relatively distant member of this family. This is the first report that a T7-like phage adaptively parasitizes in M. morganii, and this will advance our understanding of biodiversity and adaptive evolution of T7-like phages.